首页 > 最新文献

Epigenetics最新文献

英文 中文
Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma. N6-甲基腺苷相关 lncRnas 在假性剥脱性青光眼中的作用
IF 3.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI: 10.1080/15592294.2024.2348840
Jieying Guan, Xiaohong Chen, Zhidong Li, Shuifeng Deng, Aizezi Wumaier, Yuncheng Ma, Lingling Xie, Shengsong Huang, Yingting Zhu, Yehong Zhuo

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- β signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.

探讨lncRNA m6A甲基化修饰在假性角膜剥脱性青光眼(PXG)患者眼房水(AH)中的作用。选取2021年6月至2021年12月期间接受手术的开角型PXG患者。选择年龄和性别匹配的老年性白内障(ARC)患者作为对照。患者接受了详细的眼科检查。在手术过程中提取 0.05-0.1 ml AH,用于 MeRIP-Seq 和 RNA-Seq。联合分析用于筛选具有不同m6A甲基化修饰和表达的lncRNA。使用在线软件工具绘制lncRNA-miRNA-mRNA网络(ceRNA)。lncRNAs 和 mRNAs 的表达通过实时定量 PCR 进行确认。PXG组共鉴定出4151个lncRNA和4386个相关的m6A甲基化修饰峰。同样,在对照组中检测到了 2490 个 lncRNA 和 2595 个相关的 m6A 甲基化修饰峰。与 ARC 组相比,PXG 组有 234 个高甲基化和 402 个低甲基化的 m6A 峰,其差异有统计学意义(折叠变化(FC)|≥2,p 6A 甲基化和表达同时存在。m6A甲基化修饰可能影响lncRNA的表达,并通过ceRNA网络参与PXG的发病机制。ENST000000485383-hsa miR592-ROCK1 可能是进一步研究 PXG m6A 甲基化的潜在靶途径。
{"title":"Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma.","authors":"Jieying Guan, Xiaohong Chen, Zhidong Li, Shuifeng Deng, Aizezi Wumaier, Yuncheng Ma, Lingling Xie, Shengsong Huang, Yingting Zhu, Yehong Zhuo","doi":"10.1080/15592294.2024.2348840","DOIUrl":"10.1080/15592294.2024.2348840","url":null,"abstract":"<p><p>To explore the role of lncRNA m<sup>6</sup>A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m<sup>6</sup>A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m<sup>6</sup>A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m<sup>6</sup>A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m<sup>6</sup>A peaks, with statistically significant differences (| Fold Change (FC) |≥2, <i>p</i> < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- β signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m<sup>6</sup>A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m<sup>6</sup>A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m<sup>6</sup>A methylation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2348840"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
YY1/circCTNNB1/miR-186-5p/YY1 positive loop aggravates lung cancer progression through the Wnt pathway. YY1/circCTNNB1/miR-186-5p/YY1正循环通过Wnt通路加剧肺癌进展
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-24 DOI: 10.1080/15592294.2024.2369006
Yanli Shen, Yan Yang, Yan Zhao, Saiteer Nuerlan, Yiyi Zhan, Chunling Liu

Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the functions and related regulatory mechanisms of circCTNNB1 in lung cancer remain largely indistinct. The mRNA and protein expression levels were examined through real-time polymerase chain reaction (RT-qPCR) and western blot. The cell proliferation was tested through CCK-8 assay. The cell migration and invasion were confirmed through Transwell assays. The cell senescence was evaluated through SA-β-gal assay. The binding ability between miR-186-5p and circCTNNB1 (or YY1) was verified through luciferase reporter and RIP assays. In this study, the higher expression of circCTNNB1 was discovered in lung cancer tissues and cell lines and resulted in poor prognosis. In addition, circCTNNB1 facilitated lung cancer cell proliferation, migration, invasion, and suppressed cell senescence. Knockdown of circCTNNB1 retarded the Wnt pathway. Mechanism-related experiments revealed that circCTNNB1 combined with miR-186-5p to target YY1. Through rescue assays, YY1 overexpression could rescue decreased cell proliferation, migration, invasion, increased cell senescence, and retarded Wnt pathway mediated by circCTNNB1 suppression. Furthermore, YY1 acts as a transcription factor that can transcriptionally activate circCTNNB1 to form YY1/circCTNNB1/miR-186-5p/YY1 positive loop. Through in vivo assays, circCTNNB1 accelerated tumour growth in vivo. All findings revealed that a positive loop YY1/circCTNNB1/miR-186-5p/YY1 aggravated lung cancer progression by modulating the Wnt pathway.

肺癌是威胁人类生命的一种常见癌症。已有研究表明,circCTNNB1 在一些疾病中具有调控功能。然而,circCTNNB1在肺癌中的功能和相关调控机制在很大程度上仍不明确。通过实时聚合酶链式反应(RT-qPCR)和免疫印迹检测了mRNA和蛋白质的表达水平。细胞增殖通过 CCK-8 试验进行检测。细胞迁移和侵袭通过 Transwell 试验进行确认。细胞衰老通过 SA-β-gal 试验进行评估。通过荧光素酶报告和 RIP 试验验证了 miR-186-5p 与 circCTNNB1(或 YY1)的结合能力。这项研究发现,circCTNNB1 在肺癌组织和细胞系中的高表达导致了不良预后。此外,circCTNNB1 还能促进肺癌细胞增殖、迁移和侵袭,并抑制细胞衰老。敲除 circCTNNB1 可延缓 Wnt 通路。机制相关实验显示,circCTNNB1与miR-186-5p结合,靶向YY1。通过挽救实验,YY1 的过表达可以挽救由 circCTNNB1 抑制导致的细胞增殖、迁移、侵袭、细胞衰老和 Wnt 通路延缓。此外,YY1作为一种转录因子,可以转录激活circCTNNB1,形成YY1/circCTNNB1/miR-186-5p/YY1正环。通过体内试验,circCTNNB1 加快了体内肿瘤的生长。所有研究结果表明,YY1/circCTNNB1/miR-186-5p/YY1正环路通过调节Wnt通路加剧了肺癌的进展。
{"title":"YY1/circCTNNB1/miR-186-5p/YY1 positive loop aggravates lung cancer progression through the Wnt pathway.","authors":"Yanli Shen, Yan Yang, Yan Zhao, Saiteer Nuerlan, Yiyi Zhan, Chunling Liu","doi":"10.1080/15592294.2024.2369006","DOIUrl":"10.1080/15592294.2024.2369006","url":null,"abstract":"<p><p>Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the functions and related regulatory mechanisms of circCTNNB1 in lung cancer remain largely indistinct. The mRNA and protein expression levels were examined through real-time polymerase chain reaction (RT-qPCR) and western blot. The cell proliferation was tested through CCK-8 assay. The cell migration and invasion were confirmed through Transwell assays. The cell senescence was evaluated through SA-β-gal assay. The binding ability between miR-186-5p and circCTNNB1 (or YY1) was verified through luciferase reporter and RIP assays. In this study, the higher expression of circCTNNB1 was discovered in lung cancer tissues and cell lines and resulted in poor prognosis. In addition, circCTNNB1 facilitated lung cancer cell proliferation, migration, invasion, and suppressed cell senescence. Knockdown of circCTNNB1 retarded the Wnt pathway. Mechanism-related experiments revealed that circCTNNB1 combined with miR-186-5p to target YY1. Through rescue assays, YY1 overexpression could rescue decreased cell proliferation, migration, invasion, increased cell senescence, and retarded Wnt pathway mediated by circCTNNB1 suppression. Furthermore, YY1 acts as a transcription factor that can transcriptionally activate circCTNNB1 to form YY1/circCTNNB1/miR-186-5p/YY1 positive loop. Through in vivo assays, circCTNNB1 accelerated tumour growth in vivo. All findings revealed that a positive loop YY1/circCTNNB1/miR-186-5p/YY1 aggravated lung cancer progression by modulating the Wnt pathway.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2369006"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transgenerational epigenetic self-memory of Dio3 dosage is associated with Meg3 methylation and altered growth trajectories and neonatal hormones. Dio3剂量的跨代表观遗传自我记忆与Meg3甲基化以及生长轨迹和新生儿激素的改变有关。
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-11 DOI: 10.1080/15592294.2024.2376948
M Elena Martinez, Aldona Karaczyn, Zhaofei Wu, Christian A Bennett, Kassey L Matoin, Heather M Daigle, Arturo Hernandez

Intergenerational and transgenerational epigenetic effects resulting from conditions in previous generations can contribute to environmental adaptation as well as disease susceptibility. Previous studies in rodent and human models have shown that abnormal developmental exposure to thyroid hormone affects endocrine function and thyroid hormone sensitivity in later generations. Since the imprinted type 3 deiodinase gene (Dio3) regulates sensitivity to thyroid hormones, we hypothesize its epigenetic regulation is altered in descendants of thyroid hormone overexposed individuals. Using DIO3-deficient mice as a model of developmental thyrotoxicosis, we investigated Dio3 total and allelic expression and growth and endocrine phenotypes in descendants. We observed that male and female developmental overexposure to thyroid hormone altered total and allelic Dio3 expression in genetically intact descendants in a tissue-specific manner. This was associated with abnormal growth and neonatal levels of thyroid hormone and leptin. Descendant mice also exhibited molecular abnormalities in the Dlk1-Dio3 imprinted domain, including increased methylation in Meg3 and altered foetal brain expression of other genes of the Dlk1-Dio3 imprinted domain. These molecular abnormalities were also observed in the tissues and germ line of DIO3-deficient ancestors originally overexposed to thyroid hormone in utero. Our results provide a novel paradigm of epigenetic self-memory by which Dio3 gene dosage in a given individual, and its dependent developmental exposure to thyroid hormone, influences its own expression in future generations. This mechanism of epigenetic self-correction of Dio3 expression in each generation may be instrumental in descendants for their adaptive programming of developmental growth and adult endocrine function.

上一代人的状况所产生的代际和跨代表观遗传效应可能会导致环境适应性和疾病易感性。以前在啮齿动物和人类模型中进行的研究表明,发育过程中异常暴露于甲状腺激素会影响后代的内分泌功能和甲状腺激素敏感性。由于印迹3型脱碘酶基因(Dio3)调节对甲状腺激素的敏感性,我们推测甲状腺激素过度暴露者的后代对该基因的表观遗传调节会发生改变。我们利用DIO3缺陷小鼠作为发育性甲状腺毒症的模型,研究了Dio3的总表达和等位基因表达以及后代的生长和内分泌表型。我们观察到,雄性和雌性发育过程中过度暴露于甲状腺激素会以组织特异性的方式改变基因完整的后代的Dio3总表达量和等位基因表达量。这与生长异常以及新生儿甲状腺激素和瘦素水平有关。后代小鼠还表现出 Dlk1-Dio3 印记域的分子异常,包括 Meg3 的甲基化增加和 Dlk1-Dio3 印记域其他基因的胎儿脑表达改变。最初在子宫内过度暴露于甲状腺激素的DIO3缺陷祖先的组织和生殖系中也观察到了这些分子异常。我们的研究结果提供了一种新的表观遗传自我记忆范例,通过这种范例,特定个体中的Dio3基因剂量及其与甲状腺激素的依赖性发育暴露会影响其自身在后代中的表达。这种在每一代中对Dio3表达进行表观遗传自我校正的机制可能有助于后代对发育生长和成年内分泌功能进行适应性编程。
{"title":"Transgenerational epigenetic self-memory of <i>Dio3</i> dosage is associated with <i>Meg3</i> methylation and altered growth trajectories and neonatal hormones.","authors":"M Elena Martinez, Aldona Karaczyn, Zhaofei Wu, Christian A Bennett, Kassey L Matoin, Heather M Daigle, Arturo Hernandez","doi":"10.1080/15592294.2024.2376948","DOIUrl":"10.1080/15592294.2024.2376948","url":null,"abstract":"<p><p>Intergenerational and transgenerational epigenetic effects resulting from conditions in previous generations can contribute to environmental adaptation as well as disease susceptibility. Previous studies in rodent and human models have shown that abnormal developmental exposure to thyroid hormone affects endocrine function and thyroid hormone sensitivity in later generations. Since the imprinted type 3 deiodinase gene (<i>Dio3</i>) regulates sensitivity to thyroid hormones, we hypothesize its epigenetic regulation is altered in descendants of thyroid hormone overexposed individuals. Using DIO3-deficient mice as a model of developmental thyrotoxicosis, we investigated <i>Dio3</i> total and allelic expression and growth and endocrine phenotypes in descendants. We observed that male and female developmental overexposure to thyroid hormone altered total and allelic <i>Dio3</i> expression in genetically intact descendants in a tissue-specific manner. This was associated with abnormal growth and neonatal levels of thyroid hormone and leptin. Descendant mice also exhibited molecular abnormalities in the <i>Dlk1-Dio3</i> imprinted domain, including increased methylation in <i>Meg3</i> and altered foetal brain expression of other genes of the <i>Dlk1-Dio3</i> imprinted domain. These molecular abnormalities were also observed in the tissues and germ line of DIO3-deficient ancestors originally overexposed to thyroid hormone <i>in utero</i>. Our results provide a novel paradigm of epigenetic self-memory by which <i>Dio3</i> gene dosage in a given individual, and its dependent developmental exposure to thyroid hormone, influences its own expression in future generations. This mechanism of epigenetic self-correction of <i>Dio3</i> expression in each generation may be instrumental in descendants for their adaptive programming of developmental growth and adult endocrine function.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2376948"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome-wide methylation analysis in patients with proximal hypospadias - a pilot study and review of the literature. 尿道下裂近端患者的全基因组甲基化分析--一项试验性研究和文献综述。
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-08-16 DOI: 10.1080/15592294.2024.2392048
Yolande van Bever, Ruben G Boers, Hennie T Brüggenwirth, Wilfred Fj van IJcken, Frank J Magielsen, Annelies de Klein, Joachim B Boers, Leendert Hj Looijenga, Erwin Brosens, Joost Gribnau, Sabine E Hannema

In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.

在尿道下裂近端患者中,尽管进行了广泛的基因检测,但往往找不到遗传原因。许多参与性发育的基因编码转录因子,其基因产物的产生时间和剂量有严格的规定。我们假设尿道下裂男童的 DNA 甲基化可能会反复出现差异,而且这些差异可能会因患者出生时的胎龄不同而不同。我们对 16 名不明原因的尿道下裂近端 XY 男孩、1 名不明原因的 XX 睾丸疾病/性发育差异(DSD)男孩和 12 名性别和年龄匹配的健康对照者的白细胞进行了 RE 消化,然后对 32bp LpnPI 限制性酶片段进行了全基因组甲基化 DNA 测序(MeD-seq)。患者与 XY 对照组之间的七个差异甲基化区域(DMRs)中有五个位于长基因间非蛋白编码 RNA 665(LINC00665;CpG24525)。三名患者的 MAP3K1 出现了高甲基化。最后,在 XX 男孩与 XX 对照组中,没有发现 XX 睾丸 DSD 相关基因的 DMRs。总之,在 16 名 XY 近端尿道下裂男孩中,我们没有观察到可识别的表观遗传学特征,出生时身材矮小与胎龄适宜的儿童之间也没有差异。与之前针对尿道下裂患者的甲基化研究相比,我们的发现并不一致,这可能是由于采用了不同的纳入标准、组织和方法。
{"title":"Genome-wide methylation analysis in patients with proximal hypospadias - a pilot study and review of the literature.","authors":"Yolande van Bever, Ruben G Boers, Hennie T Brüggenwirth, Wilfred Fj van IJcken, Frank J Magielsen, Annelies de Klein, Joachim B Boers, Leendert Hj Looijenga, Erwin Brosens, Joost Gribnau, Sabine E Hannema","doi":"10.1080/15592294.2024.2392048","DOIUrl":"10.1080/15592294.2024.2392048","url":null,"abstract":"<p><p>In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2392048"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resistance and aerobic training increases genome-wide DNA methylation in women with polycystic ovary syndrome. 阻力训练和有氧训练可增加多囊卵巢综合征妇女的全基因组 DNA 甲基化。
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-21 DOI: 10.1080/15592294.2024.2305082
Cristiana Libardi Miranda Furtado, Megan Hansen, Gislaine Satyko Kogure, Victor Barbosa Ribeiro, Nathanael Taylor, Murilo Racy Soares, Rui Alberto Ferriani, Kenneth Ivan Aston, Timothy Jenkins, Rosana Maria Dos Reis

Physical activity is a first-line treatment for polycystic ovary syndrome (PCOS). Resistance or aerobic exercise improves metabolic complications, reproductive outcomes, and quality of life in PCOS. DNA methylation reprogramming during exercise may be the major modifier behind these changes. We sought to evaluate genome-wide DNA methylation changes after supervised resistance and aerobic exercise in women with PCOS. Exercises were performed in 56 women with PCOS (resistance, n = 30; aerobic, n = 26), for 16 weeks (wks), three times per week, in 50-minute to one-hour sessions. Anthropometric indices and hormonal and metabolic parameters were measured before and after training. Genome-wide leukocyte DNA methylation was analysed by Infinium Human MethylationEPIC 850K BeadChip microarrays (Illumina). Both resistance and aerobic exercise improved anthropometric indices, metabolic dysfunction, and hyperandrogenism in PCOS after the training programme, but no differences were observed between the two exercises. Resistance and aerobic exercise increased genome-wide DNA methylation, although resistance changed every category in the CpG island context (islands, shores, shelve, and open sea), whereas aerobic exercise altered CpG shores and the open sea. Using a stringent FDR (>40), 6 significantly differentially methylated regions (DMRs) were observed in the resistance exercise cohort and 14 DRMs in the aerobic cohort, all of which were hypermethylated. The increase in genome-wide DNA methylation may be related to the metabolic and hormonal changes observed in PCOS after resistance and aerobic exercise. Since the mammalian genome is hypermethylated globally to prevent genomic instability and ageing, resistance and aerobic exercise may promote health and longevity through environmentally induced epigenetic changes.

体育锻炼是治疗多囊卵巢综合症(PCOS)的一线疗法。阻力运动或有氧运动可改善多囊卵巢综合征的代谢并发症、生殖结果和生活质量。运动过程中的 DNA 甲基化重编程可能是这些变化背后的主要调节因素。我们试图评估患有多囊卵巢综合症的女性在进行有监督的阻力运动和有氧运动后全基因组 DNA 甲基化的变化。我们对 56 名多囊卵巢综合症女性进行了为期 16 周(周)、每周三次、每次 50 分钟至一小时的运动(阻力运动,30 人;有氧运动,26 人)。训练前后测量了人体测量指数以及激素和代谢参数。全基因组白细胞 DNA 甲基化由 Infinium Human MethylationEPIC 850K BeadChip 芯片(Illumina)进行分析。阻力运动和有氧运动都能改善多囊卵巢综合征患者的人体测量指数、代谢功能障碍和高雄激素症,但两种运动之间没有差异。阻力运动和有氧运动都增加了全基因组的DNA甲基化,但阻力运动改变了CpG岛背景(岛屿、海岸、搁置和公海)中的每个类别,而有氧运动则改变了CpG海岸和公海。使用严格的 FDR(大于 40),在阻力运动队列中观察到 6 个显著差异甲基化区域(DMR),在有氧运动队列中观察到 14 个 DRMs,所有这些区域都是高甲基化的。全基因组 DNA 甲基化的增加可能与抵抗运动和有氧运动后在多囊卵巢综合征中观察到的代谢和激素变化有关。由于哺乳动物基因组在全球范围内都存在高甲基化以防止基因组的不稳定性和老化,阻力运动和有氧运动可能会通过环境诱导的表观遗传变化促进健康和长寿。
{"title":"Resistance and aerobic training increases genome-wide DNA methylation in women with polycystic ovary syndrome.","authors":"Cristiana Libardi Miranda Furtado, Megan Hansen, Gislaine Satyko Kogure, Victor Barbosa Ribeiro, Nathanael Taylor, Murilo Racy Soares, Rui Alberto Ferriani, Kenneth Ivan Aston, Timothy Jenkins, Rosana Maria Dos Reis","doi":"10.1080/15592294.2024.2305082","DOIUrl":"10.1080/15592294.2024.2305082","url":null,"abstract":"<p><p>Physical activity is a first-line treatment for polycystic ovary syndrome (PCOS). Resistance or aerobic exercise improves metabolic complications, reproductive outcomes, and quality of life in PCOS. DNA methylation reprogramming during exercise may be the major modifier behind these changes. We sought to evaluate genome-wide DNA methylation changes after supervised resistance and aerobic exercise in women with PCOS. Exercises were performed in 56 women with PCOS (resistance, <i>n</i> = 30; aerobic, <i>n</i> = 26), for 16 weeks (wks), three times per week, in 50-minute to one-hour sessions. Anthropometric indices and hormonal and metabolic parameters were measured before and after training. Genome-wide leukocyte DNA methylation was analysed by Infinium Human MethylationEPIC 850K BeadChip microarrays (Illumina). Both resistance and aerobic exercise improved anthropometric indices, metabolic dysfunction, and hyperandrogenism in PCOS after the training programme, but no differences were observed between the two exercises. Resistance and aerobic exercise increased genome-wide DNA methylation, although resistance changed every category in the CpG island context (islands, shores, shelve, and open sea), whereas aerobic exercise altered CpG shores and the open sea. Using a stringent FDR (>40), 6 significantly differentially methylated regions (DMRs) were observed in the resistance exercise cohort and 14 DRMs in the aerobic cohort, all of which were hypermethylated. The increase in genome-wide DNA methylation may be related to the metabolic and hormonal changes observed in PCOS after resistance and aerobic exercise. Since the mammalian genome is hypermethylated globally to prevent genomic instability and ageing, resistance and aerobic exercise may promote health and longevity through environmentally induced epigenetic changes.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2305082"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Methylome profile of medaka eggs and sperm. 青鳉卵子和精子的甲基组图谱。
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-21 DOI: 10.1080/15592294.2024.2417151
Xuegeng Wang, Ramji K Bhandari

Eggs and sperm are responsible for the continuation of generations. Following the epigenetic reprogramming of the embryo, core epigenetic information present in the sperm and eggs is transmitted to offspring somatic cells prior to the blastula stage, which specifically influences gene expression in the cells. Differences in the patterns of DNA methylation between the paternal and maternal genomes are critical to regulating allele-specific gene expression in the developing embryo, constituting the basis of genomic imprinting in mammals. While the information on allele-specific epigenetic information has been limited to mammals, it is not clearly understood whether non-mammalian vertebrate gametes possess any sex-specific allelic epigenetic information and whether somatic cells maintain the allele-specific epigenetic information, particularly DNA methylation. To determine the landscape of DNA methylation in paternal and maternal alleles in a non-mammalian vertebrate, we profiled the methylome of egg in medaka fish and compared it with our previously published medaka sperm methylome. We identified a set of gamete-specific differentially methylated regions (DMRs) in the genome- medaka eggs maintained a significantly lower global methylation profile than the sperm. Based on our sequencing depth and data, 10 DMRs were hypermethylated, and 237 DMRs were hypomethylated in the eggs compared to the sperm methylome. Somatic cells in blastula maintained some of those parental gamete-specific DNA methylation profiles. Those DMRs are associated with 70 genes, suggesting that they may have imprinted-like functions and warrant further investigation.

卵子和精子负责延续世代。胚胎经过表观遗传重编程后,精子和卵子中的核心表观遗传信息会在胚泡阶段之前传递给后代体细胞,从而对细胞中的基因表达产生特定影响。父基因组和母基因组 DNA 甲基化模式的差异对于调节发育中胚胎的等位基因特异性基因表达至关重要,是哺乳动物基因组印记的基础。虽然有关等位基因特异性表观遗传信息的研究仅限于哺乳动物,但对非哺乳动物脊椎动物配子是否具有性别特异性等位基因表观遗传信息,以及体细胞是否保持等位基因特异性表观遗传信息,尤其是DNA甲基化,尚不清楚。为了确定非哺乳类脊椎动物父系和母系等位基因的DNA甲基化状况,我们分析了青鳉鱼卵的甲基组,并与之前发表的青鳉精子甲基组进行了比较。我们在基因组中发现了一组配子特异性差异甲基化区域(DMRs)--青鳉鱼卵的全局甲基化谱明显低于精子。根据我们的测序深度和数据,与精子甲基组相比,卵子中有10个DMR高甲基化,237个DMR低甲基化。胚泡中的体细胞保持了其中一些亲本配子特异的DNA甲基化图谱。这些DMRs与70个基因相关,表明它们可能具有类似印记的功能,值得进一步研究。
{"title":"Methylome profile of medaka eggs and sperm.","authors":"Xuegeng Wang, Ramji K Bhandari","doi":"10.1080/15592294.2024.2417151","DOIUrl":"10.1080/15592294.2024.2417151","url":null,"abstract":"<p><p>Eggs and sperm are responsible for the continuation of generations. Following the epigenetic reprogramming of the embryo, core epigenetic information present in the sperm and eggs is transmitted to offspring somatic cells prior to the blastula stage, which specifically influences gene expression in the cells. Differences in the patterns of DNA methylation between the paternal and maternal genomes are critical to regulating allele-specific gene expression in the developing embryo, constituting the basis of genomic imprinting in mammals. While the information on allele-specific epigenetic information has been limited to mammals, it is not clearly understood whether non-mammalian vertebrate gametes possess any sex-specific allelic epigenetic information and whether somatic cells maintain the allele-specific epigenetic information, particularly DNA methylation. To determine the landscape of DNA methylation in paternal and maternal alleles in a non-mammalian vertebrate, we profiled the methylome of egg in medaka fish and compared it with our previously published medaka sperm methylome. We identified a set of gamete-specific differentially methylated regions (DMRs) in the genome- medaka eggs maintained a significantly lower global methylation profile than the sperm. Based on our sequencing depth and data, 10 DMRs were hypermethylated, and 237 DMRs were hypomethylated in the eggs compared to the sperm methylome. Somatic cells in blastula maintained some of those parental gamete-specific DNA methylation profiles. Those DMRs are associated with 70 genes, suggesting that they may have imprinted-like functions and warrant further investigation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2417151"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA methylation variation and growth in the clonal Duchesnea indica is regulated by both past and present lead environments. Duchesnea indica克隆植物的DNA甲基化变异和生长受过去和现在铅环境的调节。
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-21 DOI: 10.1080/15592294.2024.2305078
Jiaxin Quan, Shanshan Song, Linya Xing, Xiao Liu, Ming Yue

Studies suggest that clonal plants' ability to select habitats and forage in a heterogeneous environment is influenced by their past environment, with stress legacy potentially playing a crucial role. In this study, we examined parental ramets of Duchesnea indica Focke that were subject to either a control or lead-contaminated environment (past environment), and their newborn offspring were then transplanted into control, homogeneous lead or heterogeneous lead environment (present environment). We analysed how past and present environments affect plant growth and DNA methylation in offspring. The result shown that the DNA methylation loci composition of offspring was affected by the interaction of parental environment and offspring environment, and DNA methylation levels were higher in heterogeneous environments. Moreover, our findings indicate that offspring would thrive in the heterogeneous lead environment if they did not experience lead pollution in the past, their progeny will avoid lead toxicity by reducing underground biomass allocation. However, when the parents experienced lead stress environment, their biomass allocation strategies disappeared, and they prefer to grow in favourable patches to avoid lead-contaminated patches. We concluded that the integration of historical parental exposure to lead-contaminated and current information about their offspring's environment are impacting plant phenotypes. It is possible that the stress legacy from the parents has been transmitted to their offspring ramets, and the stress legacy is at least partly based on heritable epigenetic variation. The phenotypic variation regulated by the stress legacy affects the growth performance, biomass allocation strategy, and even the behaviour of D. indica.

研究表明,克隆植物在异质环境中选择栖息地和觅食的能力受其过去环境的影响,而压力遗产可能起着至关重要的作用。在这项研究中,我们研究了受对照环境或铅污染环境(过去环境)影响的 Duchesnea indica Focke 的亲本柱头,然后将它们的新生后代移植到对照环境、同质铅环境或异质铅环境(现在环境)中。我们分析了过去和现在的环境对植物生长和后代 DNA 甲基化的影响。结果表明,子代的DNA甲基化位点组成受亲代环境和子代环境的交互影响,在异质环境中DNA甲基化水平更高。此外,我们的研究结果表明,如果亲本过去没有经历过铅污染,其后代会在异质铅环境中茁壮成长,其后代会通过减少地下生物量分配来避免铅毒性。然而,当亲本经历过铅胁迫环境时,它们的生物量分配策略就会消失,它们更愿意在有利的斑块中生长,以避开铅污染斑块。我们的结论是,亲本历史上暴露于铅污染环境的情况与子代当前所处环境的信息相结合,对植物表型产生了影响。亲本的压力遗产有可能已传递给子代植株,而压力遗产至少有一部分是基于可遗传的表观遗传变异。受胁迫遗传调节的表型变异会影响籼稻的生长表现、生物量分配策略甚至行为。
{"title":"DNA methylation variation and growth in the clonal <i>Duchesnea indica</i> is regulated by both past and present lead environments.","authors":"Jiaxin Quan, Shanshan Song, Linya Xing, Xiao Liu, Ming Yue","doi":"10.1080/15592294.2024.2305078","DOIUrl":"10.1080/15592294.2024.2305078","url":null,"abstract":"<p><p>Studies suggest that clonal plants' ability to select habitats and forage in a heterogeneous environment is influenced by their past environment, with stress legacy potentially playing a crucial role. In this study, we examined parental ramets of <i>Duchesnea indica</i> Focke that were subject to either a control or lead-contaminated environment (past environment), and their newborn offspring were then transplanted into control, homogeneous lead or heterogeneous lead environment (present environment). We analysed how past and present environments affect plant growth and DNA methylation in offspring. The result shown that the DNA methylation loci composition of offspring was affected by the interaction of parental environment and offspring environment, and DNA methylation levels were higher in heterogeneous environments. Moreover, our findings indicate that offspring would thrive in the heterogeneous lead environment if they did not experience lead pollution in the past, their progeny will avoid lead toxicity by reducing underground biomass allocation. However, when the parents experienced lead stress environment, their biomass allocation strategies disappeared, and they prefer to grow in favourable patches to avoid lead-contaminated patches. We concluded that the integration of historical parental exposure to lead-contaminated and current information about their offspring's environment are impacting plant phenotypes. It is possible that the stress legacy from the parents has been transmitted to their offspring ramets, and the stress legacy is at least partly based on heritable epigenetic variation. The phenotypic variation regulated by the stress legacy affects the growth performance, biomass allocation strategy, and even the behaviour of <i>D. indica</i>.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2305078"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Using methylation data to improve transcription factor binding prediction. 利用甲基化数据改进转录因子结合预测。
IF 3.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-01 DOI: 10.1080/15592294.2024.2309826
Daniel Morgan, Dawn L DeMeo, Kimberly Glass

Modelling the regulatory mechanisms that determine cell fate, response to external perturbation, and disease state depends on measuring many factors, a task made more difficult by the plasticity of the epigenome. Scanning the genome for the sequence patterns defined by Position Weight Matrices (PWM) can be used to estimate transcription factor (TF) binding locations. However, this approach does not incorporate information regarding the epigenetic context necessary for TF binding. CpG methylation is an epigenetic mark influenced by environmental factors that is commonly assayed in human cohort studies. We developed a framework to score inferred TF binding locations using methylation data. We intersected motif locations identified using PWMs with methylation information captured in both whole-genome bisulfite sequencing and Illumina EPIC array data for six cell lines, scored motif locations based on these data, and compared with experimental data characterizing TF binding (ChIP-seq). We found that for most TFs, binding prediction improves using methylation-based scoring compared to standard PWM-scores. We also illustrate that our approach can be generalized to infer TF binding when methylation information is only proximally available, i.e. measured for nearby CpGs that do not directly overlap with a motif location. Overall, our approach provides a framework for inferring context-specific TF binding using methylation data. Importantly, the availability of DNA methylation data in existing patient populations provides an opportunity to use our approach to understand the impact of methylation on gene regulatory processes in the context of human disease.

对决定细胞命运、对外部扰动的反应和疾病状态的调控机制建模取决于对许多因素的测量,而表观基因组的可塑性使这项任务变得更加困难。扫描基因组中由位置权重矩阵(PWM)定义的序列模式可用于估计转录因子(TF)的结合位置。然而,这种方法并不包含 TF 结合所需的表观遗传背景信息。CpG 甲基化是一种受环境因素影响的表观遗传标记,通常在人类队列研究中进行检测。我们开发了一个框架,利用甲基化数据对推断的 TF 结合位置进行评分。我们将利用 PWMs 确定的主题位置与全基因组亚硫酸氢盐测序和 Illumina EPIC 阵列数据中捕获的甲基化信息相交叉,根据这些数据对主题位置进行评分,并与表征 TF 结合的实验数据(ChIP-seq)进行比较。我们发现,与标准的 PWM 评分相比,基于甲基化的评分能改进大多数 TF 的结合预测。我们还说明,当甲基化信息只有近端可用时,我们的方法可以推广到推断 TF 的结合,即测量与主题位置不直接重叠的附近 CpGs。总之,我们的方法为利用甲基化数据推断特异性 TF 结合提供了一个框架。重要的是,现有患者群体中 DNA 甲基化数据的可用性为利用我们的方法了解甲基化在人类疾病背景下对基因调控过程的影响提供了机会。
{"title":"Using methylation data to improve transcription factor binding prediction.","authors":"Daniel Morgan, Dawn L DeMeo, Kimberly Glass","doi":"10.1080/15592294.2024.2309826","DOIUrl":"10.1080/15592294.2024.2309826","url":null,"abstract":"<p><p>Modelling the regulatory mechanisms that determine cell fate, response to external perturbation, and disease state depends on measuring many factors, a task made more difficult by the plasticity of the epigenome. Scanning the genome for the sequence patterns defined by Position Weight Matrices (PWM) can be used to estimate transcription factor (TF) binding locations. However, this approach does not incorporate information regarding the epigenetic context necessary for TF binding. CpG methylation is an epigenetic mark influenced by environmental factors that is commonly assayed in human cohort studies. We developed a framework to score inferred TF binding locations using methylation data. We intersected motif locations identified using PWMs with methylation information captured in both whole-genome bisulfite sequencing and Illumina EPIC array data for six cell lines, scored motif locations based on these data, and compared with experimental data characterizing TF binding (ChIP-seq). We found that for most TFs, binding prediction improves using methylation-based scoring compared to standard PWM-scores. We also illustrate that our approach can be generalized to infer TF binding when methylation information is only proximally available, <i>i.e</i>. measured for nearby CpGs that do not directly overlap with a motif location. Overall, our approach provides a framework for inferring context-specific TF binding using methylation data. Importantly, the availability of DNA methylation data in existing patient populations provides an opportunity to use our approach to understand the impact of methylation on gene regulatory processes in the context of human disease.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2309826"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress. miR-34/449水平的降低从精子传递到植入前胚胎是父代慢性社会不稳定压力影响的跨代表观遗传的关键步骤。
IF 3.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-13 DOI: 10.1080/15592294.2024.2346694
Alexandre Champroux, Yang Tang, David A Dickson, Alice Meng, Anne Harrington, Lucy Liaw, Matteo Marzi, Francesco Nicassio, Thorsten M Schlaeger, Larry A Feig

The transgenerational effects of exposing male mice to chronic social instability (CSI) stress are associated with decreased sperm levels of multiple members of the miR-34/449 family that persist after their mating through preimplantation embryo (PIE) development. Here we demonstrate the importance of these miRNA changes by showing that restoring miR-34c levels in PIEs derived from CSI stressed males prevents elevated anxiety and defective sociability normally found specifically in their adult female offspring. It also restores, at least partially, levels of sperm miR-34/449 normally reduced in their male offspring who transmit these sex-specific traits to their offspring. Strikingly, these experiments also revealed that inducing miR-34c levels in PIEs enhances the expression of its own gene and that of miR-449 in these cells. The same induction of embryo miR-34/449 gene expression likely occurs after sperm-derived miR-34c is introduced into oocytes upon fertilization. Thus, suppression of this miRNA amplification system when sperm miR-34c levels are reduced in CSI stressed mice can explain how a comparable fold-suppression of miR-34/449 levels can be found in PIEs derived from them, despite sperm containing ~50-fold lower levels of these miRNAs than those already present in PIEs. We previously found that men exposed to early life trauma also display reduced sperm levels of miR-34/449. And here we show that miR-34c can also increase the expression of its own gene, and that of miR-449 in human embryonic stem cells, suggesting that human PIEs derived from men with low sperm miR-34/449 levels may also contain this potentially harmful defect.

雄性小鼠暴露于慢性社会不稳定性(CSI)应激的跨代效应与 miR-34/449 家族多个成员的精子水平下降有关,这种下降在交配后通过植入前胚胎(PIE)发育持续存在。在这里,我们证明了这些 miRNA 变化的重要性,因为我们发现,恢复 CSI 应激雄性胚胎 PIE 中的 miR-34c 水平,可防止其成年雌性后代通常会出现的焦虑升高和社交能力缺陷。它还至少部分恢复了通常在雄性后代中降低的精子 miR-34/449 水平,这些雄性后代会将这些性别特异性遗传给其后代。令人震惊的是,这些实验还发现,诱导 PIE 中的 miR-34c 水平会增强其自身基因和 miR-449 在这些细胞中的表达。在受精时将来自精子的 miR-34c 导入卵母细胞后,也可能会诱导胚胎 miR-34/449 基因的表达。因此,当 CSI 胁迫小鼠的精子 miR-34c 水平降低时,这种 miRNA 扩增系统会受到抑制,这就可以解释为什么尽管精子中这些 miRNA 的水平比 PIE 中已经存在的 miRNA 水平低约 50 倍,但在由它们产生的 PIE 中却发现 miR-34/449 水平受到了类似倍数的抑制。我们以前曾发现,受到早期生活创伤的男性精子中的miR-34/449水平也会降低。我们在这里发现,miR-34c还能增加其自身基因的表达,以及人类胚胎干细胞中miR-449基因的表达,这表明从精子miR-34/449水平低的男性中提取的人类PIE也可能含有这种潜在的有害缺陷。
{"title":"Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress.","authors":"Alexandre Champroux, Yang Tang, David A Dickson, Alice Meng, Anne Harrington, Lucy Liaw, Matteo Marzi, Francesco Nicassio, Thorsten M Schlaeger, Larry A Feig","doi":"10.1080/15592294.2024.2346694","DOIUrl":"10.1080/15592294.2024.2346694","url":null,"abstract":"<p><p>The transgenerational effects of exposing male mice to chronic social instability (CSI) stress are associated with decreased sperm levels of multiple members of the miR-34/449 family that persist after their mating through preimplantation embryo (PIE) development. Here we demonstrate the importance of these miRNA changes by showing that restoring miR-34c levels in PIEs derived from CSI stressed males prevents elevated anxiety and defective sociability normally found specifically in their adult female offspring. It also restores, at least partially, levels of sperm miR-34/449 normally reduced in their male offspring who transmit these sex-specific traits to their offspring. Strikingly, these experiments also revealed that inducing miR-34c levels in PIEs enhances the expression of its own gene and that of miR-449 in these cells. The same induction of embryo miR-34/449 gene expression likely occurs after sperm-derived miR-34c is introduced into oocytes upon fertilization. Thus, suppression of this miRNA amplification system when sperm miR-34c levels are reduced in CSI stressed mice can explain how a comparable fold-suppression of miR-34/449 levels can be found in PIEs derived from them, despite sperm containing ~50-fold lower levels of these miRNAs than those already present in PIEs. We previously found that men exposed to early life trauma also display reduced sperm levels of miR-34/449. And here we show that miR-34c can also increase the expression of its own gene, and that of miR-449 in human embryonic stem cells, suggesting that human PIEs derived from men with low sperm miR-34/449 levels may also contain this potentially harmful defect.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2346694"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MK-801-exposure induces increased translation efficiency and mRNA hyperacetylation of Grin2a in the mouse prefrontal cortex. MK-801 暴露诱导小鼠前额叶皮层中 Grin2a 的翻译效率提高和 mRNA 过度乙酰化。
IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-26 DOI: 10.1080/15592294.2024.2417158
Liting Xue, Jialu Zhao, Xu Liu, Tian Zhao, Ying Zhang, Haihong Ye

Acute exposure to MK-801, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, induces schizophrenia-like behavioural changes in juvenile male mice. However, the effects of acute MK-801 exposure on brain gene expression at the translation level remain unclear. Here, we conducted ribosome profiling analysis on the prefrontal cortex (PFC) of acute MK-801-exposed juvenile male mice. We found 357 differentially translated genes, with the N4-acetylcytidine (ac4C) consensus motif enriched in the transcripts with increased translation efficiency. Acetylated RNA immunoprecipitation sequencing revealed 148 differentially acetylated peaks, of which 121 were hyperacetylated, and 27 were hypoacetylated. Genes harbouring these peaks were enriched in pathways related to axon guidance, Hedgehog signalling pathway, neuron differentiation, and memory. Grin2a encodes an NMDA receptor subunit NMDAR2A, and its human orthologue is a strong susceptibility gene for schizophrenia. Grin2a mRNA was hyperacetylated and exhibited significantly increased translation efficiency. NMDAR2A protein level was increased in MK-801-exposed PFC. Pretreatment of Remodelin, an inhibitor of N-acetyltransferase 10, returned the NMDAR2A protein levels to normal and partially reversed schizophrenia-like behaviours of MK-801-exposed mice, shedding light on the possible role of mRNA acetylation in the aetiology of schizophrenia.

急性暴露于非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂MK-801可诱导幼年雄性小鼠出现类似精神分裂症的行为变化。然而,急性 MK-801 暴露在翻译水平上对大脑基因表达的影响仍不清楚。在这里,我们对急性暴露于 MK-801 的幼年雄性小鼠的前额叶皮层(PFC)进行了核糖体图谱分析。我们发现了 357 个翻译不同的基因,其中 N4-乙酰胞苷(ac4C)共识基团富集在翻译效率提高的转录本中。乙酰化 RNA 免疫沉淀测序发现了 148 个不同的乙酰化峰,其中 121 个为高乙酰化,27 个为低乙酰化。含有这些峰的基因富集在与轴突导向、刺猬信号通路、神经元分化和记忆有关的通路中。Grin2a编码NMDA受体亚基NMDAR2A,其人类同源物是精神分裂症的强易感基因。Grin2a mRNA被过度乙酰化,翻译效率显著提高。在 MK-801 暴露的全脑功能区,NMDAR2A 蛋白水平升高。使用N-乙酰转移酶10抑制剂Remodelin预处理后,NMDAR2A蛋白水平恢复正常,并部分逆转了MK-801暴露小鼠的精神分裂症样行为,从而揭示了mRNA乙酰化在精神分裂症病因中可能扮演的角色。
{"title":"MK-801-exposure induces increased translation efficiency and mRNA hyperacetylation of <i>Grin2a</i> in the mouse prefrontal cortex.","authors":"Liting Xue, Jialu Zhao, Xu Liu, Tian Zhao, Ying Zhang, Haihong Ye","doi":"10.1080/15592294.2024.2417158","DOIUrl":"10.1080/15592294.2024.2417158","url":null,"abstract":"<p><p>Acute exposure to MK-801, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, induces schizophrenia-like behavioural changes in juvenile male mice. However, the effects of acute MK-801 exposure on brain gene expression at the translation level remain unclear. Here, we conducted ribosome profiling analysis on the prefrontal cortex (PFC) of acute MK-801-exposed juvenile male mice. We found 357 differentially translated genes, with the <i>N</i><sup>4</sup>-acetylcytidine (ac<sup>4</sup>C) consensus motif enriched in the transcripts with increased translation efficiency. Acetylated RNA immunoprecipitation sequencing revealed 148 differentially acetylated peaks, of which 121 were hyperacetylated, and 27 were hypoacetylated. Genes harbouring these peaks were enriched in pathways related to axon guidance, Hedgehog signalling pathway, neuron differentiation, and memory. <i>Grin2a</i> encodes an NMDA receptor subunit NMDAR2A, and its human orthologue is a strong susceptibility gene for schizophrenia. <i>Grin2a</i> mRNA was hyperacetylated and exhibited significantly increased translation efficiency. NMDAR2A protein level was increased in MK-801-exposed PFC. Pretreatment of Remodelin, an inhibitor of <i>N</i>-acetyltransferase 10, returned the NMDAR2A protein levels to normal and partially reversed schizophrenia-like behaviours of MK-801-exposed mice, shedding light on the possible role of mRNA acetylation in the aetiology of schizophrenia.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2417158"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Epigenetics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1