Background: Identification of potential drug-target interactions (DTIs) with high accuracy is a key step in drug discovery and repositioning, especially concerning specific drug targets. Traditional experimental methods for identifying the DTIs are arduous, time-intensive, and financially burdensome. In addition, robust computational methods have been developed for predicting the DTIs and are widely applied in drug discovery research. However, advancing more precise algorithms for predicting DTIs is essential to meet the stringent standards demanded by drug discovery.
Results: We proposed a novel method called GSRF-DTI, which integrates networks with a deep learning algorithm to identify DTIs. Firstly, GSRF-DTI learned the embedding representation of drugs and targets by integrating multiple drug association information and target association information, respectively. Then, GSRF-DTI considered the influence of drug-target pair (DTP) association on DTI prediction to construct a drug-target pair network (DTP-NET). Next, we utilized GraphSAGE on DTP-NET to learn the potential features of the network and applied random forest (RF) to predict the DTIs. Furthermore, we conducted ablation experiments to validate the necessity of integrating different types of network features for identifying DTIs. It is worth noting that GSRF-DTI proposed three novel DTIs.
Conclusions: GSRF-DTI not only considered the influence of the interaction relationship between drug and target but also considered the impact of DTP association relationship on DTI prediction. We initially use GraphSAGE to aggregate the neighbor information of nodes for better identification. Experimental analysis on Luo's dataset and the newly constructed dataset revealed that the GSRF-DTI framework outperformed several state-of-the-art methods significantly.
{"title":"GSRF-DTI: a framework for drug-target interaction prediction based on a drug-target pair network and representation learning on a large graph.","authors":"Yongdi Zhu, Chunhui Ning, Naiqian Zhang, Mingyi Wang, Yusen Zhang","doi":"10.1186/s12915-024-01949-3","DOIUrl":"10.1186/s12915-024-01949-3","url":null,"abstract":"<p><strong>Background: </strong>Identification of potential drug-target interactions (DTIs) with high accuracy is a key step in drug discovery and repositioning, especially concerning specific drug targets. Traditional experimental methods for identifying the DTIs are arduous, time-intensive, and financially burdensome. In addition, robust computational methods have been developed for predicting the DTIs and are widely applied in drug discovery research. However, advancing more precise algorithms for predicting DTIs is essential to meet the stringent standards demanded by drug discovery.</p><p><strong>Results: </strong>We proposed a novel method called GSRF-DTI, which integrates networks with a deep learning algorithm to identify DTIs. Firstly, GSRF-DTI learned the embedding representation of drugs and targets by integrating multiple drug association information and target association information, respectively. Then, GSRF-DTI considered the influence of drug-target pair (DTP) association on DTI prediction to construct a drug-target pair network (DTP-NET). Next, we utilized GraphSAGE on DTP-NET to learn the potential features of the network and applied random forest (RF) to predict the DTIs. Furthermore, we conducted ablation experiments to validate the necessity of integrating different types of network features for identifying DTIs. It is worth noting that GSRF-DTI proposed three novel DTIs.</p><p><strong>Conclusions: </strong>GSRF-DTI not only considered the influence of the interaction relationship between drug and target but also considered the impact of DTP association relationship on DTI prediction. We initially use GraphSAGE to aggregate the neighbor information of nodes for better identification. Experimental analysis on Luo's dataset and the newly constructed dataset revealed that the GSRF-DTI framework outperformed several state-of-the-art methods significantly.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mounting evidence shows that tumor-derived extracellular vesicles (EVs) are critical constituents in the tumor microenvironment. The composition and function of EVs often change during cancer progression. However, it remains less clear how cancer cells modulate their own EV biogenesis to promote tumor development. The release of EVs is closely linked to the endolysosome system residing within the cell. The current study aims to decipher the role of endosomal protein DENND10 in cancer development. Bioinformatics data mining showed that DENND10 expression is significantly associated with poor prognosis in multiple cancer types and up-regulated in metastatic breast cancer cell lines. DENND10 knockout (DENND10-KO) in breast cancer cells led to defective EV biogenesis due to impaired endolysosomal trafficking. Intriguingly, DENND10-KO cells exhibited reductions in cell spreading, migration, invasion, and metastatic potential in vivo. These deficiencies in cell motility were associated with compromised cytoskeleton organization. Importantly, wild-type conditioned medium or EVs restored the migratory ability and cytoskeletal organization of DENND10-KO cells. Global proteomic profiling revealed that DENND10 depletion led to a distinct EV compositional landscape with remodeled profiles of extracellular matrix (ECM) and adhesion molecules. Consistently, exogenous application of ECM molecules rescued the spreading and migration of DENND10-KO cells. In summary, our study unveiled DENND10 as an intrinsic regulator of cell migration that modifies the tumor microenvironment through autocrine EV release, which could be exploited for developing targeted therapies for tumor metastasis.
{"title":"Endosomal protein DENND10/FAM45A integrates extracellular vesicle release with cancer cell migration","authors":"Shenqing Sun, Qian Li, Ganggang Liu, Xiaoheng Huang, Aiqing Li, Haoran Guo, Lijuan Qi, Jie Zhang, Jianrui Song, Xiong Su, Yanling Zhang","doi":"10.1186/s12915-024-01948-4","DOIUrl":"https://doi.org/10.1186/s12915-024-01948-4","url":null,"abstract":"Mounting evidence shows that tumor-derived extracellular vesicles (EVs) are critical constituents in the tumor microenvironment. The composition and function of EVs often change during cancer progression. However, it remains less clear how cancer cells modulate their own EV biogenesis to promote tumor development. The release of EVs is closely linked to the endolysosome system residing within the cell. The current study aims to decipher the role of endosomal protein DENND10 in cancer development. Bioinformatics data mining showed that DENND10 expression is significantly associated with poor prognosis in multiple cancer types and up-regulated in metastatic breast cancer cell lines. DENND10 knockout (DENND10-KO) in breast cancer cells led to defective EV biogenesis due to impaired endolysosomal trafficking. Intriguingly, DENND10-KO cells exhibited reductions in cell spreading, migration, invasion, and metastatic potential in vivo. These deficiencies in cell motility were associated with compromised cytoskeleton organization. Importantly, wild-type conditioned medium or EVs restored the migratory ability and cytoskeletal organization of DENND10-KO cells. Global proteomic profiling revealed that DENND10 depletion led to a distinct EV compositional landscape with remodeled profiles of extracellular matrix (ECM) and adhesion molecules. Consistently, exogenous application of ECM molecules rescued the spreading and migration of DENND10-KO cells. In summary, our study unveiled DENND10 as an intrinsic regulator of cell migration that modifies the tumor microenvironment through autocrine EV release, which could be exploited for developing targeted therapies for tumor metastasis.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141575226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1186/s12915-024-01951-9
Yanke Jiang, Yingzhe Yue, Chongchong Lu, Muhammad Zunair Latif, Haifeng Liu, Zhaoxu Wang, Ziyi Yin, Yang Li, Xinhua Ding
Pre-mRNA splicing is a significant step for post-transcriptional modifications and functions in a wide range of physiological processes in plants. Human NHP2L binds to U4 snRNA during spliceosome assembly; it is involved in RNA splicing and mediates the development of human tumors. However, no ortholog has yet been identified in plants. Therefore, we report At4g12600 encoding the ortholog NHP2L protein, and AtSNU13 associates with the component of the spliceosome complex; the atsnu13 mutant showed compromised resistance in disease resistance, indicating that AtSNU13 is a positive regulator of plant immunity. Compared to wild-type plants, the atsnu13 mutation resulted in altered splicing patterns for defense-related genes and decreased expression of defense-related genes, such as RBOHD and ALD1. Further investigation shows that AtSNU13 promotes the interaction between U4/U6.U5 tri-snRNP-specific 27 K and the motif in target mRNAs to regulate the RNA splicing. Our study highlights the role of AtSNU13 in regulating plant immunity by affecting the pre-mRNA splicing of defense-related genes.
{"title":"AtSNU13 modulates pre-mRNA splicing of RBOHD and ALD1 to regulate plant immunity.","authors":"Yanke Jiang, Yingzhe Yue, Chongchong Lu, Muhammad Zunair Latif, Haifeng Liu, Zhaoxu Wang, Ziyi Yin, Yang Li, Xinhua Ding","doi":"10.1186/s12915-024-01951-9","DOIUrl":"10.1186/s12915-024-01951-9","url":null,"abstract":"<p><p>Pre-mRNA splicing is a significant step for post-transcriptional modifications and functions in a wide range of physiological processes in plants. Human NHP2L binds to U4 snRNA during spliceosome assembly; it is involved in RNA splicing and mediates the development of human tumors. However, no ortholog has yet been identified in plants. Therefore, we report At4g12600 encoding the ortholog NHP2L protein, and AtSNU13 associates with the component of the spliceosome complex; the atsnu13 mutant showed compromised resistance in disease resistance, indicating that AtSNU13 is a positive regulator of plant immunity. Compared to wild-type plants, the atsnu13 mutation resulted in altered splicing patterns for defense-related genes and decreased expression of defense-related genes, such as RBOHD and ALD1. Further investigation shows that AtSNU13 promotes the interaction between U4/U6.U5 tri-snRNP-specific 27 K and the motif in target mRNAs to regulate the RNA splicing. Our study highlights the role of AtSNU13 in regulating plant immunity by affecting the pre-mRNA splicing of defense-related genes.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1186/s12915-024-01954-6
Kaifang Wang, Huijuan Xu, Rong Zou, Guangqun Zeng, Ye Yuan, Xianjun Zhu, Xiaohui Zhao, Jie Li, Lin Zhang
Author Correction: BMC Biology 22, 134 (2024)
https://doi.org/10.1186/s12915-024-01932-y
The original article [1] mistakenly attributes co-author, Xiaohui Zhao to affiliation #3; Xioahui Zhao should instead be affiliated to affiliation #2.
Wang K, et al. PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina. BMC Biol. 2024;22:134. https://doi.org/10.1186/s12915-024-01932-y.
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Authors and Affiliations
The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, School of Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China
Kaifang Wang, Huijuan Xu, Rong Zou, Xianjun Zhu, Jie Li & Lin Zhang
Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, Qinghai, China
Huijuan Xu, Xianjun Zhu, Xiaohui Zhao & Lin Zhang
The People’s Hospital of Pengzhou, Chengdu, 611930, Sichuan, China
Guangqun Zeng
Medical Center Hospital of Qionglai City, Chengdu, 611530, Sichuan, China
Ye Yuan
Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, China
Xianjun Zhu & Lin Zhang
Department of Ophthalmology, School of Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China
Jie Li
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作者更正:BMC Biology 22, 134 (2024)https://doi.org/10.1186/s12915-024-01932-yThe 原文[1]误将合著者赵晓辉归属于3号单位;赵晓辉应归属于2号单位。Wang K, et al. PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina.BMC Biol. 2024;22:134. https://doi.org/10.1186/s12915-024-01932-y.文章 CAS PubMed PubMed Central Google Scholar 下载参考文献作者及单位电子科技大学四川省人民医院医学院医学遗传学中心人类疾病基因研究四川省重点实验室,四川成都610072王开芳,徐慧娟,邹蓉,朱先军,李杰&;张琳 中国科学院西北高原生物研究所藏医药研究省级重点实验室,青海,西宁,810008 徐慧娟,朱贤军,赵晓辉 &;张林 四川省成都市彭州市人民医院 四川,611930 曾广群 四川省成都市邛崃市医学中心医院 四川,611530 袁晔 四川省医学科学院、四川省人民医院中国医学科学院防盲研究室(2019RU026) 四川,610072 朱贤君 &;张琳电子科技大学医学院、四川省人民医院眼科,四川成都,610072ChinaJie Li作者:王开芳查看作者发表论文您也可以在PubMed Google Scholar中搜索该作者徐慧娟查看作者发表论文您也可以在PubMed Google Scholar中搜索该作者邹蓉查看作者发表论文您也可以在PubMed Google Scholar中搜索该作者曾广群查看作者发表论文您也可以在PubMed Google Scholar中搜索该作者袁晔查看作者发表论文您也可以在PubMed Google Scholar中搜索该作者您也可以在PubMed Google Scholar中搜索该作者朱向军查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者赵晓辉查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者李杰查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者张林查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者通讯作者:赵晓辉、李杰 或 张琳开放存取 本文采用知识共享署名 4.0 国际许可协议进行许可,该协议允许以任何媒介或格式使用、共享、改编、分发和复制本文,但需注明原作者和出处,提供知识共享许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,您需要直接从版权所有者处获得许可。如需查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明,否则创作共用公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Wang, K., Xu, H., Zou, R. et al. Author Correction:PCYT1A 缺乏会干扰小鼠视网膜的脂肪酸代谢并诱导铁变态反应。BMC Biol 22, 155 (2024). https://doi.org/10.1186/s12915-024-01954-6Download citationPublished: 10 July 2024DOI: https://doi.org/10.1186/s12915-024-01954-6Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"Author Correction: PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina","authors":"Kaifang Wang, Huijuan Xu, Rong Zou, Guangqun Zeng, Ye Yuan, Xianjun Zhu, Xiaohui Zhao, Jie Li, Lin Zhang","doi":"10.1186/s12915-024-01954-6","DOIUrl":"https://doi.org/10.1186/s12915-024-01954-6","url":null,"abstract":"<p><b>Author Correction: BMC Biology 22, 134 (2024)</b></p><p><b>https://doi.org/10.1186/s12915-024-01932-y</b></p><br/><p>The original article [1] mistakenly attributes co-author, Xiaohui Zhao to affiliation #3; Xioahui Zhao should instead be affiliated to affiliation #2.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Wang K, et al. PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina. BMC Biol. 2024;22:134. https://doi.org/10.1186/s12915-024-01932-y.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, School of Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China</p><p>Kaifang Wang, Huijuan Xu, Rong Zou, Xianjun Zhu, Jie Li & Lin Zhang</p></li><li><p>Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, Qinghai, China</p><p>Huijuan Xu, Xianjun Zhu, Xiaohui Zhao & Lin Zhang</p></li><li><p>The People’s Hospital of Pengzhou, Chengdu, 611930, Sichuan, China</p><p>Guangqun Zeng</p></li><li><p>Medical Center Hospital of Qionglai City, Chengdu, 611530, Sichuan, China</p><p>Ye Yuan</p></li><li><p>Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, China</p><p>Xianjun Zhu & Lin Zhang</p></li><li><p>Department of Ophthalmology, School of Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China</p><p>Jie Li</p></li></ol><span>Authors</span><ol><li><span>Kaifang Wang</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Huijuan Xu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Rong Zou</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Guangqun Zeng</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ye Yuan</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xianjun Zhu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </s","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141575225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1186/s12915-024-01947-5
Muzaffer Ahmad Kassab, Yibin Chen, Xin Wang, Bo He, Eric J Brown, Xiaochun Yu
Background: RNA-DNA hybrids or R-loops are associated with deleterious genomic instability and protective immunoglobulin class switch recombination (CSR). However, the underlying phenomenon regulating the two contrasting functions of R-loops is unknown. Notably, the underlying mechanism that protects R-loops from classic RNase H-mediated digestion thereby promoting persistence of CSR-associated R-loops during CSR remains elusive.
Results: Here, we report that during CSR, R-loops formed at the immunoglobulin heavy (IgH) chain are modified by ribose 2'-O-methylation (2'-OMe). Moreover, we find that 2'-O-methyltransferase fibrillarin (FBL) interacts with activation-induced cytidine deaminase (AID) associated snoRNA aSNORD1C to facilitate the 2'-OMe. Moreover, deleting AID C-terminal tail impairs its association with aSNORD1C and FBL. Disrupting FBL, AID or aSNORD1C expression severely impairs 2'-OMe, R-loop stability and CSR. Surprisingly, FBL, AID's interaction partner and aSNORD1C promoted AID targeting to the IgH locus.
Conclusion: Taken together, our results suggest that 2'-OMe stabilizes IgH-associated R-loops to enable productive CSR. These results would shed light on AID-mediated CSR and explain the mechanism of R-loop-associated genomic instability.
背景:RNA-DNA杂交或R环与有害的基因组不稳定性和保护性免疫球蛋白类开关重组(CSR)有关。然而,调节 R 环两种截然不同功能的基本现象尚不清楚。值得注意的是,在 CSR 过程中,保护 R 环不受典型 RNase H 介导的消化,从而促进 CSR 相关 R 环持续存在的潜在机制仍不清楚:在此,我们报告了在 CSR 期间,免疫球蛋白重链(IgH)上形成的 R 环被核糖 2'-O- 甲基化(2'-OMe)修饰。此外,我们还发现,2'-O-甲基转移酶纤维蛋白素(FBL)与活化诱导胞苷脱氨酶(AID)相关的 snoRNA aSNORD1C 相互作用,促进了 2'-OMe 的发生。此外,删除 AID C 端尾部会削弱其与 aSNORD1C 和 FBL 的关联。破坏 FBL、AID 或 aSNORD1C 的表达会严重影响 2'-Ome、R-环稳定性和 CSR。令人惊讶的是,FBL、AID的相互作用伙伴和aSNORD1C促进了AID靶向IgH基因座:综上所述,我们的研究结果表明,2'-OMe能稳定IgH相关的R环,从而实现富有成效的CSR。这些结果将揭示 AID 介导的 CSR,并解释 R 环相关基因组不稳定性的机制。
{"title":"RNA 2'-O-methylation promotes persistent R-loop formation and AID-mediated IgH class switch recombination.","authors":"Muzaffer Ahmad Kassab, Yibin Chen, Xin Wang, Bo He, Eric J Brown, Xiaochun Yu","doi":"10.1186/s12915-024-01947-5","DOIUrl":"10.1186/s12915-024-01947-5","url":null,"abstract":"<p><strong>Background: </strong>RNA-DNA hybrids or R-loops are associated with deleterious genomic instability and protective immunoglobulin class switch recombination (CSR). However, the underlying phenomenon regulating the two contrasting functions of R-loops is unknown. Notably, the underlying mechanism that protects R-loops from classic RNase H-mediated digestion thereby promoting persistence of CSR-associated R-loops during CSR remains elusive.</p><p><strong>Results: </strong>Here, we report that during CSR, R-loops formed at the immunoglobulin heavy (IgH) chain are modified by ribose 2'-O-methylation (2'-OMe). Moreover, we find that 2'-O-methyltransferase fibrillarin (FBL) interacts with activation-induced cytidine deaminase (AID) associated snoRNA aSNORD1C to facilitate the 2'-OMe. Moreover, deleting AID C-terminal tail impairs its association with aSNORD1C and FBL. Disrupting FBL, AID or aSNORD1C expression severely impairs 2'-OMe, R-loop stability and CSR. Surprisingly, FBL, AID's interaction partner and aSNORD1C promoted AID targeting to the IgH locus.</p><p><strong>Conclusion: </strong>Taken together, our results suggest that 2'-OMe stabilizes IgH-associated R-loops to enable productive CSR. These results would shed light on AID-mediated CSR and explain the mechanism of R-loop-associated genomic instability.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1186/s12915-024-01950-w
Yuncong Zhang, Yu Yang, Liping Ren, Meixiao Zhan, Taoping Sun, Quan Zou, Yang Zhang
Background: Metabolite-associated cell communications play critical roles in maintaining human biological function. However, most existing tools and resources focus only on ligand-receptor interaction pairs where both partners are proteinaceous, neglecting other non-protein molecules. To address this gap, we introduce the MRCLinkdb database and algorithm, which aggregates and organizes data related to non-protein L-R interactions in cell-cell communication, providing a valuable resource for predicting intercellular communication based on metabolite-related ligand-receptor interactions.
Results: Here, we manually curated the metabolite-ligand-receptor (ML-R) interactions from the literature and known databases, ultimately collecting over 790 human and 670 mouse ML-R interactions. Additionally, we compiled information on over 1900 enzymes and 260 transporter entries associated with these metabolites. We developed Metabolite-Receptor based Cell Link Database (MRCLinkdb) to store these ML-R interactions data. Meanwhile, the platform also offers extensive information for presenting ML-R interactions, including fundamental metabolite information and the overall expression landscape of metabolite-associated gene sets (such as receptor, enzymes, and transporter proteins) based on single-cell transcriptomics sequencing (covering 35 human and 26 mouse tissues, 52 human and 44 mouse cell types) and bulk RNA-seq/microarray data (encompassing 62 human and 39 mouse tissues). Furthermore, MRCLinkdb introduces a web server dedicated to the analysis of intercellular communication based on ML-R interactions. MRCLinkdb is freely available at https://www.cellknowledge.com.cn/mrclinkdb/ .
Conclusions: In addition to supplementing ligand-receptor databases, MRCLinkdb may provide new perspectives for decoding the intercellular communication and advancing related prediction tools based on ML-R interactions.
{"title":"Predicting intercellular communication based on metabolite-related ligand-receptor interactions with MRCLinkdb.","authors":"Yuncong Zhang, Yu Yang, Liping Ren, Meixiao Zhan, Taoping Sun, Quan Zou, Yang Zhang","doi":"10.1186/s12915-024-01950-w","DOIUrl":"10.1186/s12915-024-01950-w","url":null,"abstract":"<p><strong>Background: </strong>Metabolite-associated cell communications play critical roles in maintaining human biological function. However, most existing tools and resources focus only on ligand-receptor interaction pairs where both partners are proteinaceous, neglecting other non-protein molecules. To address this gap, we introduce the MRCLinkdb database and algorithm, which aggregates and organizes data related to non-protein L-R interactions in cell-cell communication, providing a valuable resource for predicting intercellular communication based on metabolite-related ligand-receptor interactions.</p><p><strong>Results: </strong>Here, we manually curated the metabolite-ligand-receptor (ML-R) interactions from the literature and known databases, ultimately collecting over 790 human and 670 mouse ML-R interactions. Additionally, we compiled information on over 1900 enzymes and 260 transporter entries associated with these metabolites. We developed Metabolite-Receptor based Cell Link Database (MRCLinkdb) to store these ML-R interactions data. Meanwhile, the platform also offers extensive information for presenting ML-R interactions, including fundamental metabolite information and the overall expression landscape of metabolite-associated gene sets (such as receptor, enzymes, and transporter proteins) based on single-cell transcriptomics sequencing (covering 35 human and 26 mouse tissues, 52 human and 44 mouse cell types) and bulk RNA-seq/microarray data (encompassing 62 human and 39 mouse tissues). Furthermore, MRCLinkdb introduces a web server dedicated to the analysis of intercellular communication based on ML-R interactions. MRCLinkdb is freely available at https://www.cellknowledge.com.cn/mrclinkdb/ .</p><p><strong>Conclusions: </strong>In addition to supplementing ligand-receptor databases, MRCLinkdb may provide new perspectives for decoding the intercellular communication and advancing related prediction tools based on ML-R interactions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1186/s12915-024-01941-x
Joris Lehmann, Yannick Günzel, Maryam Khosravian, Sina Cassau, Susanne Kraus, Johanna S Libnow, Hetan Chang, Bill S Hansson, Heinz Breer, Einat Couzin-Fuchs, Joerg Fleischer, Jürgen Krieger
Background: Accurate detection of pheromones is crucial for chemical communication and reproduction in insects. In holometabolous flies and moths, the sensory neuron membrane protein 1 (SNMP1) is essential for detecting long-chain aliphatic pheromones by olfactory neurons. However, its function in hemimetabolous insects and its role for detecting pheromones of a different chemical nature remain elusive. Therefore, we investigated the relevance of SNMP1 for pheromone detection in a hemimetabolous insect pest of considerable economic importance, the desert locust Schistocerca gregaria, which moreover employs the aromatic pheromone phenylacetonitrile (PAN) to govern reproductive behaviors.
Results: Employing CRISPR/Cas-mediated gene editing, a mutant locust line lacking functional SNMP1 was established. In electroantennography experiments and single sensillum recordings, we found significantly decreased electrical responses to PAN in SNMP1-deficient (SNMP1-/-) locusts. Moreover, calcium imaging in the antennal lobe of the brain revealed a substantially reduced activation of projection neurons in SNMP1-/- individuals upon exposure to PAN, indicating that the diminished antennal responsiveness to PAN in mutants affects pheromone-evoked neuronal activity in the brain. Furthermore, in behavioral experiments, PAN-induced effects on pairing and mate choice were altered in SNMP1-/- locusts.
Conclusions: Our findings emphasize the importance of SNMP1 for chemical communication in a hemimetabolous insect pest. Moreover, they show that SNMP1 plays a crucial role in pheromone detection that goes beyond long-chain aliphatic substances and includes aromatic compounds controlling reproductive behaviors.
{"title":"SNMP1 is critical for sensitive detection of the desert locust aromatic courtship inhibition pheromone phenylacetonitrile.","authors":"Joris Lehmann, Yannick Günzel, Maryam Khosravian, Sina Cassau, Susanne Kraus, Johanna S Libnow, Hetan Chang, Bill S Hansson, Heinz Breer, Einat Couzin-Fuchs, Joerg Fleischer, Jürgen Krieger","doi":"10.1186/s12915-024-01941-x","DOIUrl":"10.1186/s12915-024-01941-x","url":null,"abstract":"<p><strong>Background: </strong>Accurate detection of pheromones is crucial for chemical communication and reproduction in insects. In holometabolous flies and moths, the sensory neuron membrane protein 1 (SNMP1) is essential for detecting long-chain aliphatic pheromones by olfactory neurons. However, its function in hemimetabolous insects and its role for detecting pheromones of a different chemical nature remain elusive. Therefore, we investigated the relevance of SNMP1 for pheromone detection in a hemimetabolous insect pest of considerable economic importance, the desert locust Schistocerca gregaria, which moreover employs the aromatic pheromone phenylacetonitrile (PAN) to govern reproductive behaviors.</p><p><strong>Results: </strong>Employing CRISPR/Cas-mediated gene editing, a mutant locust line lacking functional SNMP1 was established. In electroantennography experiments and single sensillum recordings, we found significantly decreased electrical responses to PAN in SNMP1-deficient (SNMP1<sup>-/-</sup>) locusts. Moreover, calcium imaging in the antennal lobe of the brain revealed a substantially reduced activation of projection neurons in SNMP1<sup>-/-</sup> individuals upon exposure to PAN, indicating that the diminished antennal responsiveness to PAN in mutants affects pheromone-evoked neuronal activity in the brain. Furthermore, in behavioral experiments, PAN-induced effects on pairing and mate choice were altered in SNMP1<sup>-/-</sup> locusts.</p><p><strong>Conclusions: </strong>Our findings emphasize the importance of SNMP1 for chemical communication in a hemimetabolous insect pest. Moreover, they show that SNMP1 plays a crucial role in pheromone detection that goes beyond long-chain aliphatic substances and includes aromatic compounds controlling reproductive behaviors.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1186/s12915-024-01945-7
Amanda N Scholes, Tara N Stuecker, Stephanie E Hood, Cader J Locke, Carson L Stacy, Qingyang Zhang, Jeffrey A Lewis
Background: Organisms frequently experience environmental stresses that occur in predictable patterns and combinations. For wild Saccharomyces cerevisiae yeast growing in natural environments, cells may experience high osmotic stress when they first enter broken fruit, followed by high ethanol levels during fermentation, and then finally high levels of oxidative stress resulting from respiration of ethanol. Yeast have adapted to these patterns by evolving sophisticated "cross protection" mechanisms, where mild 'primary' doses of one stress can enhance tolerance to severe doses of a different 'secondary' stress. For example, in many yeast strains, mild osmotic or mild ethanol stresses cross protect against severe oxidative stress, which likely reflects an anticipatory response important for high fitness in nature.
Results: During the course of genetic mapping studies aimed at understanding the mechanisms underlying natural variation in ethanol-induced cross protection against H2O2, we found that a key H2O2 scavenging enzyme, cytosolic catalase T (Ctt1p), was absolutely essential for cross protection in a wild oak strain. This suggested the absence of other compensatory mechanisms for acquiring H2O2 resistance in that strain background under those conditions. In this study, we found surprising heterogeneity across diverse yeast strains in whether CTT1 function was fully necessary for acquired H2O2 resistance. Some strains exhibited partial dispensability of CTT1 when ethanol and/or salt were used as mild stressors, suggesting that compensatory peroxidases may play a role in acquired stress resistance in certain genetic backgrounds. We leveraged global transcriptional responses to ethanol and salt stresses in strains with different levels of CTT1 dispensability, allowing us to identify possible regulators of these alternative peroxidases and acquired stress resistance in general.
Conclusions: Ultimately, this study highlights how superficially similar traits can have different underlying molecular foundations and provides a framework for understanding the diversity and regulation of stress defense mechanisms.
{"title":"Natural variation in yeast reveals multiple paths for acquiring higher stress resistance.","authors":"Amanda N Scholes, Tara N Stuecker, Stephanie E Hood, Cader J Locke, Carson L Stacy, Qingyang Zhang, Jeffrey A Lewis","doi":"10.1186/s12915-024-01945-7","DOIUrl":"10.1186/s12915-024-01945-7","url":null,"abstract":"<p><strong>Background: </strong>Organisms frequently experience environmental stresses that occur in predictable patterns and combinations. For wild Saccharomyces cerevisiae yeast growing in natural environments, cells may experience high osmotic stress when they first enter broken fruit, followed by high ethanol levels during fermentation, and then finally high levels of oxidative stress resulting from respiration of ethanol. Yeast have adapted to these patterns by evolving sophisticated \"cross protection\" mechanisms, where mild 'primary' doses of one stress can enhance tolerance to severe doses of a different 'secondary' stress. For example, in many yeast strains, mild osmotic or mild ethanol stresses cross protect against severe oxidative stress, which likely reflects an anticipatory response important for high fitness in nature.</p><p><strong>Results: </strong>During the course of genetic mapping studies aimed at understanding the mechanisms underlying natural variation in ethanol-induced cross protection against H<sub>2</sub>O<sub>2</sub>, we found that a key H<sub>2</sub>O<sub>2</sub> scavenging enzyme, cytosolic catalase T (Ctt1p), was absolutely essential for cross protection in a wild oak strain. This suggested the absence of other compensatory mechanisms for acquiring H<sub>2</sub>O<sub>2</sub> resistance in that strain background under those conditions. In this study, we found surprising heterogeneity across diverse yeast strains in whether CTT1 function was fully necessary for acquired H<sub>2</sub>O<sub>2</sub> resistance. Some strains exhibited partial dispensability of CTT1 when ethanol and/or salt were used as mild stressors, suggesting that compensatory peroxidases may play a role in acquired stress resistance in certain genetic backgrounds. We leveraged global transcriptional responses to ethanol and salt stresses in strains with different levels of CTT1 dispensability, allowing us to identify possible regulators of these alternative peroxidases and acquired stress resistance in general.</p><p><strong>Conclusions: </strong>Ultimately, this study highlights how superficially similar traits can have different underlying molecular foundations and provides a framework for understanding the diversity and regulation of stress defense mechanisms.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1186/s12915-024-01937-7
Sanasar G Babajanyan, Sofya K Garushyants, Yuri I Wolf, Eugene V Koonin
Background: Microbiomes are generally characterized by high diversity of coexisting microbial species and strains, and microbiome composition typically remains stable across a broad range of conditions. However, under fixed conditions, microbial ecology conforms with the exclusion principle under which two populations competing for the same resource within the same niche cannot coexist because the less fit population inevitably goes extinct. Therefore, the long-term persistence of microbiome diversity calls for an explanation.
Results: To explore the conditions for stabilization of microbial diversity, we developed a simple mathematical model consisting of two competing populations that could exchange a single gene allele via horizontal gene transfer (HGT). We found that, although in a fixed environment, with unbiased HGT, the system obeyed the exclusion principle, in an oscillating environment, within large regions of the phase space bounded by the rates of reproduction and HGT, the two populations coexist. Moreover, depending on the parameter combination, all three major types of symbiosis were obtained, namely, pure competition, host-parasite relationship, and mutualism. In each of these regimes, certain parameter combinations provided for synergy, that is, a greater total abundance of both populations compared to the abundance of the winning population in the fixed environment.
Conclusions: The results of this modeling study show that basic phenomena that are universal in microbial communities, namely, environmental variation and HGT, provide for stabilization and persistence of microbial diversity, and emergence of ecological complexity.
{"title":"Microbial diversity and ecological complexity emerging from environmental variation and horizontal gene transfer in a simple mathematical model.","authors":"Sanasar G Babajanyan, Sofya K Garushyants, Yuri I Wolf, Eugene V Koonin","doi":"10.1186/s12915-024-01937-7","DOIUrl":"10.1186/s12915-024-01937-7","url":null,"abstract":"<p><strong>Background: </strong>Microbiomes are generally characterized by high diversity of coexisting microbial species and strains, and microbiome composition typically remains stable across a broad range of conditions. However, under fixed conditions, microbial ecology conforms with the exclusion principle under which two populations competing for the same resource within the same niche cannot coexist because the less fit population inevitably goes extinct. Therefore, the long-term persistence of microbiome diversity calls for an explanation.</p><p><strong>Results: </strong>To explore the conditions for stabilization of microbial diversity, we developed a simple mathematical model consisting of two competing populations that could exchange a single gene allele via horizontal gene transfer (HGT). We found that, although in a fixed environment, with unbiased HGT, the system obeyed the exclusion principle, in an oscillating environment, within large regions of the phase space bounded by the rates of reproduction and HGT, the two populations coexist. Moreover, depending on the parameter combination, all three major types of symbiosis were obtained, namely, pure competition, host-parasite relationship, and mutualism. In each of these regimes, certain parameter combinations provided for synergy, that is, a greater total abundance of both populations compared to the abundance of the winning population in the fixed environment.</p><p><strong>Conclusions: </strong>The results of this modeling study show that basic phenomena that are universal in microbial communities, namely, environmental variation and HGT, provide for stabilization and persistence of microbial diversity, and emergence of ecological complexity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1186/s12915-024-01938-6
Carla Geiger, Maria Needhamsen, Eric B Emanuelsson, Jessica Norrbom, Karen Steindorf, Carl Johan Sundberg, Stefan M Reitzner, Malene E Lindholm
Background: Physical activity is well known for its multiple health benefits and although the knowledge of the underlying molecular mechanisms is increasing, our understanding of the role of epigenetics in long-term training adaptation remains incomplete. In this intervention study, we included individuals with a history of > 15 years of regular endurance or resistance training compared to age-matched untrained controls performing endurance or resistance exercise. We examined skeletal muscle DNA methylation of genes involved in key adaptation processes, including myogenesis, gene regulation, angiogenesis and metabolism.
Results: A greater number of differentially methylated regions and differentially expressed genes were identified when comparing the endurance group with the control group than in the comparison between the strength group and the control group at baseline. Although the cellular composition of skeletal muscle samples was generally consistent across groups, variations were observed in the distribution of muscle fiber types. Slow-twitch fiber type genes MYH7 and MYL3 exhibited lower promoter methylation and elevated expression in endurance-trained athletes, while the same group showed higher methylation in transcription factors such as FOXO3, CREB5, and PGC-1α. The baseline DNA methylation state of those genes was associated with the transcriptional response to an acute bout of exercise. Acute exercise altered very few of the investigated CpG sites.
Conclusions: Endurance- compared to resistance-trained athletes and untrained individuals demonstrated a different DNA methylation signature of selected skeletal muscle genes, which may influence transcriptional dynamics following a bout of acute exercise. Skeletal muscle fiber type distribution is associated with methylation of fiber type specific genes. Our results suggest that the baseline DNA methylation landscape in skeletal muscle influences the transcription of regulatory genes in response to an acute exercise bout.
背景:体育锻炼对健康的多种益处众所周知,尽管对其潜在分子机制的了解在不断增加,但我们对表观遗传学在长期训练适应中的作用的认识仍不全面。在这项干预研究中,我们将有 15 年以上定期耐力或阻力训练史的个体与进行耐力或阻力运动的年龄匹配的未受训对照组进行了比较。我们检测了骨骼肌DNA甲基化基因的情况,这些基因涉及肌肉生成、基因调控、血管生成和新陈代谢等关键适应过程:结果:耐力组与对照组相比,发现了更多不同甲基化区域和不同表达基因;力量组与对照组相比,发现了更多不同甲基化区域和不同表达基因。虽然各组骨骼肌样本的细胞组成基本一致,但在肌肉纤维类型的分布上却出现了差异。耐力训练运动员的慢肌纤维类型基因 MYH7 和 MYL3 的启动子甲基化程度较低,表达量较高,而同一组别中 FOXO3、CREB5 和 PGC-1α 等转录因子的甲基化程度较高。这些基因的基线DNA甲基化状态与急性运动时的转录反应有关。急性运动改变的CpG位点很少:结论:耐力训练运动员与抗阻力训练运动员和未受过训练的人相比,所选骨骼肌基因的 DNA 甲基化特征不同,这可能会影响急性运动后的转录动态。骨骼肌纤维类型分布与特定纤维类型基因的甲基化有关。我们的研究结果表明,骨骼肌的基线 DNA 甲基化状况会影响调控基因在急性运动后的转录。
{"title":"DNA methylation of exercise-responsive genes differs between trained and untrained men.","authors":"Carla Geiger, Maria Needhamsen, Eric B Emanuelsson, Jessica Norrbom, Karen Steindorf, Carl Johan Sundberg, Stefan M Reitzner, Malene E Lindholm","doi":"10.1186/s12915-024-01938-6","DOIUrl":"10.1186/s12915-024-01938-6","url":null,"abstract":"<p><strong>Background: </strong>Physical activity is well known for its multiple health benefits and although the knowledge of the underlying molecular mechanisms is increasing, our understanding of the role of epigenetics in long-term training adaptation remains incomplete. In this intervention study, we included individuals with a history of > 15 years of regular endurance or resistance training compared to age-matched untrained controls performing endurance or resistance exercise. We examined skeletal muscle DNA methylation of genes involved in key adaptation processes, including myogenesis, gene regulation, angiogenesis and metabolism.</p><p><strong>Results: </strong>A greater number of differentially methylated regions and differentially expressed genes were identified when comparing the endurance group with the control group than in the comparison between the strength group and the control group at baseline. Although the cellular composition of skeletal muscle samples was generally consistent across groups, variations were observed in the distribution of muscle fiber types. Slow-twitch fiber type genes MYH7 and MYL3 exhibited lower promoter methylation and elevated expression in endurance-trained athletes, while the same group showed higher methylation in transcription factors such as FOXO3, CREB5, and PGC-1α. The baseline DNA methylation state of those genes was associated with the transcriptional response to an acute bout of exercise. Acute exercise altered very few of the investigated CpG sites.</p><p><strong>Conclusions: </strong>Endurance- compared to resistance-trained athletes and untrained individuals demonstrated a different DNA methylation signature of selected skeletal muscle genes, which may influence transcriptional dynamics following a bout of acute exercise. Skeletal muscle fiber type distribution is associated with methylation of fiber type specific genes. Our results suggest that the baseline DNA methylation landscape in skeletal muscle influences the transcription of regulatory genes in response to an acute exercise bout.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}