首页 > 最新文献

Gene regulation and systems biology最新文献

英文 中文
Biology of the Mi-2/NuRD Complex in SLAC (Stemness, Longevity/Ageing, and Cancer). Mi-2/NuRD复合体在SLAC(干性、长寿/衰老和癌症)中的生物学作用。
Pub Date : 2011-02-27 DOI: 10.4137/GRSB.S6510
Yue Zhang

The dynamic chromatin activities of Mi-2/Nucleosome Remodeling and Histone deacetylation (Mi-2/NuRD) complexes in mammals are at the basis of current research on stemness, longevity/ageing, and cancer (4-2-1/SLAC), and have been widely studied over the past decade in mammals and the elegant model organism, Caenorhabditis elegans. Interestingly, a common emergent theme from these studies is that of distinct coregulator-recruited Mi-2/NuRD complexes largely orchestrating the 4-2-1/SLAC within a unique paradigm by maintaining genome stability via DNA repair and controlling three types of transcriptional programs in concert in a number of cellular, tissue, and organism contexts. Thus, the core Mi-2/NuRD complex plays a central role in 4-2-1/SLAC. The plasticity and robustness of 4-2-1/SLAC can be interpreted as modulation of specific coregulator(s) within cell-specific, tissue-specific, stage-specific, or organism-specific niches during stress induction, ie, a functional module and its networking, thereby conferring differential responses to different environmental cues. According to "Occam's razor", a simple theory is preferable to a complex one, so this simplified notion might be useful for exploring 4-2-1/SLAC with a holistic view. This thought could also be valuable in forming strategies for future research, and could open up avenues for cancer prevention and antiageing strategies.

哺乳动物中Mi-2/核小体重塑和组蛋白去乙酰化(Mi-2/NuRD)复合物的动态染色质活性是当前研究干性、长寿/衰老和癌症(4-2-1/SLAC)的基础,并且在过去十年中在哺乳动物和优雅的模式生物秀丽隐杆线虫中得到了广泛的研究。有趣的是,这些研究中出现的一个共同主题是,不同的协同调节因子募集的Mi-2/NuRD复合物在一个独特的范例中,通过DNA修复维持基因组稳定性,并在许多细胞、组织和生物体环境中协同控制三种类型的转录程序,从而在很大程度上协调4-2-1/SLAC。因此,核心Mi-2/NuRD复合体在4-2-1/SLAC中起着核心作用。4-2-1/SLAC的可塑性和稳稳性可以解释为在应激诱导过程中,细胞特异性、组织特异性、阶段特异性或生物特异性生态位(即功能模块及其网络)中特定协同调节因子的调节,从而赋予对不同环境信号的不同反应。根据“奥卡姆剃刀”,一个简单的理论比一个复杂的理论更受欢迎,所以这个简化的概念可能对从整体角度探索4-2-1/SLAC很有用。这一想法在形成未来研究策略方面也很有价值,并可能为癌症预防和抗衰老策略开辟道路。
{"title":"Biology of the Mi-2/NuRD Complex in SLAC (Stemness, Longevity/Ageing, and Cancer).","authors":"Yue Zhang","doi":"10.4137/GRSB.S6510","DOIUrl":"https://doi.org/10.4137/GRSB.S6510","url":null,"abstract":"<p><p>The dynamic chromatin activities of Mi-2/Nucleosome Remodeling and Histone deacetylation (Mi-2/NuRD) complexes in mammals are at the basis of current research on stemness, longevity/ageing, and cancer (4-2-1/SLAC), and have been widely studied over the past decade in mammals and the elegant model organism, Caenorhabditis elegans. Interestingly, a common emergent theme from these studies is that of distinct coregulator-recruited Mi-2/NuRD complexes largely orchestrating the 4-2-1/SLAC within a unique paradigm by maintaining genome stability via DNA repair and controlling three types of transcriptional programs in concert in a number of cellular, tissue, and organism contexts. Thus, the core Mi-2/NuRD complex plays a central role in 4-2-1/SLAC. The plasticity and robustness of 4-2-1/SLAC can be interpreted as modulation of specific coregulator(s) within cell-specific, tissue-specific, stage-specific, or organism-specific niches during stress induction, ie, a functional module and its networking, thereby conferring differential responses to different environmental cues. According to \"Occam's razor\", a simple theory is preferable to a complex one, so this simplified notion might be useful for exploring 4-2-1/SLAC with a holistic view. This thought could also be valuable in forming strategies for future research, and could open up avenues for cancer prevention and antiageing strategies.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":" ","pages":"1-26"},"PeriodicalIF":0.0,"publicationDate":"2011-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S6510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29840998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts. 小鼠心脏SRF过表达调控基因中新的SRF结合位点的鉴定。
Pub Date : 2011-01-01 Epub Date: 2011-07-12 DOI: 10.4137/GRSB.S7457
Xiaomin Zhang, Gohar Azhar, Scott Helms, Brian Burton, Chris Huang, Ying Zhong, Xuesong Gu, Hong Fang, Weida Tong, Jeanne Y Wei

Background: To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg).

Methodology: Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well.

Conclusion and significance: SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart.

背景:为了在体内鉴定血清反应因子(SRF)在基因中的新的心脏结合位点,并研究这些基因对SRF轻度过表达的反应,我们采用了一种具有心脏特异性的转基因小鼠模型,SRF轻度过表达(mild - o SRF Tg)。方法:对6个月大的Mild-O-SRF Tg的心脏进行微阵列实验。我们确定了207个对心脏功能重要的基因,这些基因在体内存在差异表达。其中192个基因的启动子区存在SRF结合基序,即典型的CArG或CArG样(CArG- l)元件。56个具有经典SRF结合位点的基因中有51个以前没有报道过。这些srf调节基因根据其功能分为12类。观察到与心脏能量代谢相关的基因从脂肪酸代谢基因向碳水化合物代谢基因转移。参与转录和离子调控的基因表达减少,但细胞骨架基因的表达显著增加。利用小鼠血流动力学应激模型的公共数据库(GEO数据库),我们还发现在这些心脏缺血或主动脉收缩的心脏中也发生了类似的srf调节基因表达的改变。结论及意义:srf调控基因在多种生理病理条件下均受到积极调控。我们发现大量心脏基因具有经典的SRF结合位点,并且在Mild-O-SRF Tg小鼠心脏中被显著调节。因此,在典型的成人衰老过程中观察到的心脏中SRF蛋白的轻度升高可能对许多SRF调节基因产生重大影响,从而影响心脏的结构和性能。我们的研究结果可以帮助我们加深对SRF调节老年心脏细胞过程的理解。
{"title":"Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.","authors":"Xiaomin Zhang,&nbsp;Gohar Azhar,&nbsp;Scott Helms,&nbsp;Brian Burton,&nbsp;Chris Huang,&nbsp;Ying Zhong,&nbsp;Xuesong Gu,&nbsp;Hong Fang,&nbsp;Weida Tong,&nbsp;Jeanne Y Wei","doi":"10.4137/GRSB.S7457","DOIUrl":"https://doi.org/10.4137/GRSB.S7457","url":null,"abstract":"<p><strong>Background: </strong>To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg).</p><p><strong>Methodology: </strong>Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well.</p><p><strong>Conclusion and significance: </strong>SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":" ","pages":"41-59"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S7457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30035007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni. 曼氏血吸虫中编码通用应激蛋白的基因的发育调控
Pub Date : 2011-01-01 Epub Date: 2011-09-19 DOI: 10.4137/GRSB.S7491
Raphael D Isokpehi, Ousman Mahmud, Andreas N Mbah, Shaneka S Simmons, Lívia Avelar, Rajendram V Rajnarayanan, Udensi K Udensi, Wellington K Ayensu, Hari H Cohly, Shyretha D Brown, Centdrika R Dates, Sonya D Hentz, Shawntae J Hughes, Dominique R Smith-McInnis, Carvey O Patterson, Jennifer N Sims, Kelisha T Turner, Baraka S Williams, Matilda O Johnson, Taiwo Adubi, Judith V Mbuh, Chiaka I Anumudu, Grace O Adeoye, Bolaji N Thomas, Oyekanmi Nashiru, Guilherme Oliveira

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts.

曼氏血吸虫(Schistosoma mansoni)是一种通过蜗牛传播的二形寄生虫,其核基因组序列草案揭示了八个编码含有通用应激蛋白(USP)结构域的蛋白质的基因。曼氏血吸虫是人类血吸虫病的病原体,这是一种严重的致残性贫困被忽视热带病(NTD),在至少 76 个国家流行。血吸虫基因组序列的获得为相关基因家族的生物信息学和基因组学分析提供了机会,这些基因家族可能成为了解血吸虫病生态学、干预、预防和控制的目标。众所周知,具有 USP 结构域的蛋白质使细菌、古菌、真菌、原生生物和植物能够应对各种环境压力。在这项研究调查中,首先验证了 USP 基因的功能注释以及预测的核苷酸和蛋白质序列。随后,确定了序列群和序列的显著特征。根据与詹纳氏甲烷球菌(Methanocaldococcus jannaschii)的 ATP 结合通用应激蛋白的比对,共预测出 12 个配体结合位点。此外,六个 USP 序列显示存在 ATP 结合基序残基,表明它们可能受 ATP 调节。公有领域的基因表达数据和 RT-PCR 检测证实,曼氏沙门氏菌的所有 USP 基因在该蠕虫的至少一个发育生命周期阶段都有转录。其中 6 个基因在蛛蚴期被上调,蛛蚴期是自由游动阶段,对于向蜗牛中间宿主的传播至关重要。可能在蜗牛体内阶段,曼氏蠕虫通用应激蛋白的基因转录本含量较低,在环境应激因素(如蜗牛血细胞中存在的过氧化氢导致的氧化应激)的诱导下,曼氏蠕虫通用应激蛋白的基因转录本发挥特殊功能。本报告有助于促进研究人员网络的形成,以了解血吸虫及其钉螺中间宿主基因组中编码的通用应激蛋白的功能和调控。
{"title":"Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni.","authors":"Raphael D Isokpehi, Ousman Mahmud, Andreas N Mbah, Shaneka S Simmons, Lívia Avelar, Rajendram V Rajnarayanan, Udensi K Udensi, Wellington K Ayensu, Hari H Cohly, Shyretha D Brown, Centdrika R Dates, Sonya D Hentz, Shawntae J Hughes, Dominique R Smith-McInnis, Carvey O Patterson, Jennifer N Sims, Kelisha T Turner, Baraka S Williams, Matilda O Johnson, Taiwo Adubi, Judith V Mbuh, Chiaka I Anumudu, Grace O Adeoye, Bolaji N Thomas, Oyekanmi Nashiru, Guilherme Oliveira","doi":"10.4137/GRSB.S7491","DOIUrl":"10.4137/GRSB.S7491","url":null,"abstract":"<p><p>The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"5 ","pages":"61-74"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9562927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Application of structure equation modeling for inferring a serial transcriptional regulation in yeast. 结构方程模型在酵母一系列转录调控推断中的应用。
Pub Date : 2011-01-01 Epub Date: 2011-11-10 DOI: 10.4137/GRSB.S7569
Sachiyo Aburatani

Revealing the gene regulatory systems among DNA and proteins in living cells is one of the central aims of systems biology. In this study, I used Structural Equation Modeling (SEM) in combination with stepwise factor analysis to infer the protein-DNA interactions for gene expression control from only gene expression profiles, in the absence of protein information. I applied my approach to infer the causalities within the well-studied serial transcriptional regulation composed of GAL-related genes in yeast. This allowed me to reveal the hierarchy of serial transcriptional regulation, including previously unclear protein-DNA interactions. The validity of the constructed model was demonstrated by comparing the results with previous reports describing the regulation of the transcription factors. Furthermore, the model revealed combinatory regulation by Gal4p and Gal80p. In this study, the target genes were divided into three types: those regulated by one factor and those controlled by a combination of two factors.

揭示活细胞中DNA和蛋白质之间的基因调控系统是系统生物学的中心目标之一。在本研究中,我使用结构方程模型(SEM)结合逐步因子分析,在缺乏蛋白质信息的情况下,仅从基因表达谱推断基因表达控制的蛋白质- dna相互作用。我运用我的方法来推断在酵母中由gal相关基因组成的经过充分研究的系列转录调控中的因果关系。这使我能够揭示序列转录调控的层次结构,包括以前不清楚的蛋白质- dna相互作用。通过将结果与先前描述转录因子调控的报告进行比较,证明了所构建模型的有效性。此外,该模型还揭示了Gal4p和Gal80p的组合调控。本研究将靶基因分为单因子调控型和双因子联合调控型三种。
{"title":"Application of structure equation modeling for inferring a serial transcriptional regulation in yeast.","authors":"Sachiyo Aburatani","doi":"10.4137/GRSB.S7569","DOIUrl":"https://doi.org/10.4137/GRSB.S7569","url":null,"abstract":"<p><p>Revealing the gene regulatory systems among DNA and proteins in living cells is one of the central aims of systems biology. In this study, I used Structural Equation Modeling (SEM) in combination with stepwise factor analysis to infer the protein-DNA interactions for gene expression control from only gene expression profiles, in the absence of protein information. I applied my approach to infer the causalities within the well-studied serial transcriptional regulation composed of GAL-related genes in yeast. This allowed me to reveal the hierarchy of serial transcriptional regulation, including previously unclear protein-DNA interactions. The validity of the constructed model was demonstrated by comparing the results with previous reports describing the regulation of the transcription factors. Furthermore, the model revealed combinatory regulation by Gal4p and Gal80p. In this study, the target genes were divided into three types: those regulated by one factor and those controlled by a combination of two factors.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":" ","pages":"75-88"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S7569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30408571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Biomolecular self-defense and futility of high-specificity therapeutic targeting. 生物分子自卫和高特异性靶向治疗的无效性。
Pub Date : 2011-01-01 Epub Date: 2011-11-21 DOI: 10.4137/GRSB.S8542
Simon Rosenfeld

Robustness has been long recognized to be a distinctive property of living entities. While a reasonably wide consensus has been achieved regarding the conceptual meaning of robustness, the biomolecular mechanisms underlying this systemic property are still open to many unresolved questions. The goal of this paper is to provide an overview of existing approaches to characterization of robustness in mathematically sound terms. The concept of robustness is discussed in various contexts including network vulnerability, nonlinear dynamic stability, and self-organization. The second goal is to discuss the implications of biological robustness for individual-target therapeutics and possible strategies for outsmarting drug resistance arising from it. Special attention is paid to the concept of swarm intelligence, a well studied mechanism of self-organization in natural, societal and artificial systems. It is hypothesized that swarm intelligence is the key to understanding the emergent property of chemoresistance.

长期以来,稳健性一直被认为是生物实体的独特属性。虽然关于稳健性的概念意义已经达成了相当广泛的共识,但这种系统特性背后的生物分子机制仍有许多未解决的问题。本文的目的是提供一个概述现有的方法来表征稳健性在数学上合理的条款。鲁棒性的概念在网络脆弱性、非线性动态稳定性和自组织等不同的背景下被讨论。第二个目标是讨论生物稳健性对个体靶点治疗的影响,以及战胜由此产生的耐药性的可能策略。特别关注群体智能的概念,这是一种在自然、社会和人工系统中得到充分研究的自组织机制。假设群体智能是理解化学耐药性涌现特性的关键。
{"title":"Biomolecular self-defense and futility of high-specificity therapeutic targeting.","authors":"Simon Rosenfeld","doi":"10.4137/GRSB.S8542","DOIUrl":"https://doi.org/10.4137/GRSB.S8542","url":null,"abstract":"<p><p>Robustness has been long recognized to be a distinctive property of living entities. While a reasonably wide consensus has been achieved regarding the conceptual meaning of robustness, the biomolecular mechanisms underlying this systemic property are still open to many unresolved questions. The goal of this paper is to provide an overview of existing approaches to characterization of robustness in mathematically sound terms. The concept of robustness is discussed in various contexts including network vulnerability, nonlinear dynamic stability, and self-organization. The second goal is to discuss the implications of biological robustness for individual-target therapeutics and possible strategies for outsmarting drug resistance arising from it. Special attention is paid to the concept of swarm intelligence, a well studied mechanism of self-organization in natural, societal and artificial systems. It is hypothesized that swarm intelligence is the key to understanding the emergent property of chemoresistance.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":" ","pages":"89-104"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S8542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30408572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Molecular Cloning of the Genes Encoding the PR55/Bβ/δ Regulatory Subunits for PP-2A and Analysis of Their Functions in Regulating Development of Goldfish, Carassius auratus. PP-2A PR55/Bβ/δ调控亚基基因的克隆及其在鲫鱼发育调控中的功能分析
Pub Date : 2010-12-20 DOI: 10.4137/GRSB.S6065
Jun-Qiong Zhao, Si-Si Xie, Wen-Bin Liu, Ya-Mei Xiao, Xiao-Ming Zeng, Mi Deng, Lili Gong, Jin-Ping Liu, Pei-Chao Chen, Jie Zhou, Xiao-Hui Hu, Jia-Han Lv, Xiang-Qian Yu, Dao Wang, Chi Li, Yun-Lei Peng, Gao-Peng Liao, Yun Liu, David Wan-Cheng Li

The protein phosphatase-2A (PP-2A), one of the major phosphatases in eukaryotes, is a heterotrimer, consisting of a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits encoded by more than 16 different genes, may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the PR55/B family regulatory subunits: β and δ, analyzed their tissue specific and developmental expression patterns in Goldfish ( Carassius auratus). Our results revealed that the full-length cDNA for PR55/Bβ consists of 1940 bp with an open reading frame of 1332 nucleotides coding for a deduced protein of 443 amino acids. The full length PR55/Bδ cDNA is 2163 bp containing an open reading frame of 1347 nucleotides encoding a deduced protein of 448 amino acids. The two isoforms of PR55/B display high levels of sequence identity with their counterparts in other species. The PR55/Bβ mRNA and protein are detected in brain and heart. In contrast, the PR55/Bδ is expressed in all 9 tissues examined at both mRNA and protein levels. During development of goldfish, the mRNAs for PR55/Bβ and PR55/Bδ show distinct patterns. At the protein level, PR55/Bδ is expressed at all developmental stages examined, suggesting its important role in regulating goldfish development. Expression of the PR55/Bδ anti-sense RNA leads to significant downregulation of PR55/Bδ proteins and caused severe abnormality in goldfish trunk and eye development. Together, our results suggested that PR55/Bδ plays an important role in governing normal trunk and eye formation during goldfish development.

蛋白磷酸酶-2A(PP-2A)是真核生物中主要的磷酸酶之一,是一种异源三聚体,由支架a亚基、催化C亚基和调节B亚基组成。先前的研究表明,除了调节特定的PP-2A活性外,由超过16个不同基因编码的各种B亚基还可能具有其他功能。为了探索PP-2A调控亚基在脊椎动物发育中的可能作用,我们克隆了PR55/B家族调控亚基:β和δ,分析了它们在金鱼(Carassius auratus)中的组织特异性和发育表达模式。我们的结果表明,PR55/Bβ的全长cDNA由1940bp组成,具有1332个核苷酸的开放阅读框,编码443个氨基酸的推导蛋白质。全长PR55/BδcDNA全长2163bp,包含1347个核苷酸的开放阅读框,编码448个氨基酸的推导蛋白质。PR55/B的两个亚型与其他物种的对应物显示出高水平的序列同一性。在脑和心脏中检测到PR55/BβmRNA和蛋白。相反,PR55/Bδ在所有9个组织中均在mRNA和蛋白质水平上表达。在金鱼的发育过程中,PR55/Bβ和PR55/Bδ的mRNA表现出不同的模式。在蛋白质水平上,PR55/Bδ在所有发育阶段都有表达,这表明它在调节金鱼发育中发挥着重要作用。PR55/Bδ反义RNA的表达导致PR55/BΔ蛋白的显著下调,并导致金鱼躯干和眼睛发育的严重异常。总之,我们的研究结果表明,PR55/Bδ在金鱼发育过程中对正常的躯干和眼睛形成起着重要作用。
{"title":"Molecular Cloning of the Genes Encoding the PR55/Bβ/δ Regulatory Subunits for PP-2A and Analysis of Their Functions in Regulating Development of Goldfish, Carassius auratus.","authors":"Jun-Qiong Zhao,&nbsp;Si-Si Xie,&nbsp;Wen-Bin Liu,&nbsp;Ya-Mei Xiao,&nbsp;Xiao-Ming Zeng,&nbsp;Mi Deng,&nbsp;Lili Gong,&nbsp;Jin-Ping Liu,&nbsp;Pei-Chao Chen,&nbsp;Jie Zhou,&nbsp;Xiao-Hui Hu,&nbsp;Jia-Han Lv,&nbsp;Xiang-Qian Yu,&nbsp;Dao Wang,&nbsp;Chi Li,&nbsp;Yun-Lei Peng,&nbsp;Gao-Peng Liao,&nbsp;Yun Liu,&nbsp;David Wan-Cheng Li","doi":"10.4137/GRSB.S6065","DOIUrl":"10.4137/GRSB.S6065","url":null,"abstract":"<p><p>The protein phosphatase-2A (PP-2A), one of the major phosphatases in eukaryotes, is a heterotrimer, consisting of a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits encoded by more than 16 different genes, may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the PR55/B family regulatory subunits: β and δ, analyzed their tissue specific and developmental expression patterns in Goldfish ( Carassius auratus). Our results revealed that the full-length cDNA for PR55/Bβ consists of 1940 bp with an open reading frame of 1332 nucleotides coding for a deduced protein of 443 amino acids. The full length PR55/Bδ cDNA is 2163 bp containing an open reading frame of 1347 nucleotides encoding a deduced protein of 448 amino acids. The two isoforms of PR55/B display high levels of sequence identity with their counterparts in other species. The PR55/Bβ mRNA and protein are detected in brain and heart. In contrast, the PR55/Bδ is expressed in all 9 tissues examined at both mRNA and protein levels. During development of goldfish, the mRNAs for PR55/Bβ and PR55/Bδ show distinct patterns. At the protein level, PR55/Bδ is expressed at all developmental stages examined, suggesting its important role in regulating goldfish development. Expression of the PR55/Bδ anti-sense RNA leads to significant downregulation of PR55/Bδ proteins and caused severe abnormality in goldfish trunk and eye development. Together, our results suggested that PR55/Bδ plays an important role in governing normal trunk and eye formation during goldfish development.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"135-48"},"PeriodicalIF":0.0,"publicationDate":"2010-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S6065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29608621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Identifying a Transcription Factor's Regulatory Targets from its Binding Targets. 从结合靶标中识别转录因子的调控靶标。
Pub Date : 2010-12-08 DOI: 10.4137/GRSB.S6458
Fred Lai, Julie S Chang, Wei-Sheng Wu

ChIP-chip data, which shows binding of transcription factors (TFs) to promoter regions in vivo, are widely used by biologists to identify the regulatory targets of TFs. However, the binding of a TF to a gene does not necessarily imply regulation. Thus, it is important to develop computational methods which can extract a TF's regulatory targets from its binding targets. We developed a method, called REgulatory Targets Extraction Algorithm (RETEA), which uses partial correlation analysis on gene expression data to extract a TF's regulatory targets from its binding targets inferred from ChIP-chip data. We applied RETEA to yeast cell cycle microarray data and identified the plausible regulatory targets of eleven known cell cycle TFs. We validated our predictions by checking the enrichments for cell cycle-regulated genes, common cellular processes and common molecular functions. Finally, we showed that RETEA performs better than three published methods (MA-Network, TRIA and Garten et al's method).

ChIP-chip数据显示了转录因子(tf)在体内与启动子区域的结合,被生物学家广泛用于鉴定tf的调控靶点。然而,TF与基因的结合并不一定意味着调控。因此,开发能够从结合靶标中提取TF调控靶标的计算方法是很重要的。我们开发了一种称为调控靶标提取算法(RETEA)的方法,该方法使用基因表达数据的偏相关分析从ChIP-chip数据推断的TF结合靶标中提取出TF的调控靶标。我们将RETEA应用于酵母细胞周期微阵列数据,并确定了11个已知细胞周期tf的合理调控靶点。我们通过检查细胞周期调节基因、共同细胞过程和共同分子功能的富集程度来验证我们的预测。最后,我们发现RETEA的性能优于三种已发表的方法(MA-Network, TRIA和Garten等人的方法)。
{"title":"Identifying a Transcription Factor's Regulatory Targets from its Binding Targets.","authors":"Fred Lai,&nbsp;Julie S Chang,&nbsp;Wei-Sheng Wu","doi":"10.4137/GRSB.S6458","DOIUrl":"https://doi.org/10.4137/GRSB.S6458","url":null,"abstract":"<p><p>ChIP-chip data, which shows binding of transcription factors (TFs) to promoter regions in vivo, are widely used by biologists to identify the regulatory targets of TFs. However, the binding of a TF to a gene does not necessarily imply regulation. Thus, it is important to develop computational methods which can extract a TF's regulatory targets from its binding targets. We developed a method, called REgulatory Targets Extraction Algorithm (RETEA), which uses partial correlation analysis on gene expression data to extract a TF's regulatory targets from its binding targets inferred from ChIP-chip data. We applied RETEA to yeast cell cycle microarray data and identified the plausible regulatory targets of eleven known cell cycle TFs. We validated our predictions by checking the enrichments for cell cycle-regulated genes, common cellular processes and common molecular functions. Finally, we showed that RETEA performs better than three published methods (MA-Network, TRIA and Garten et al's method).</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"125-33"},"PeriodicalIF":0.0,"publicationDate":"2010-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S6458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29608620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Alpha-Tocopherol Modulates Transcriptional Activities that Affect Essential Biological Processes in Bovine Cells. α -生育酚调节影响牛细胞基本生物过程的转录活性。
Pub Date : 2010-11-22 DOI: 10.4137/GRSB.S6007
Cong-Jun Li, Robert W Li, Theodore H Elsasser

Using global expression profiling and pathway analysis on α-tocopherol-induced gene perturbation in bovine cells, this study has generated comprehensive information on the physiological functions of α-tocopherol. The data confirmed α-tocopherol is a potent regulator of gene expression and α-tocopherol possesses novel transcriptional activities that affect essential biological processes. The genes identified fall within a broad range of functional categories and provide the molecular basis for its distinctive effects. Enrichment analyses of gene regulatory networks indicate α-tocopherol alter the canonical pathway of lipid metabolism and transcription factors SREBP1 and SREBP2, (Sterol regulatory element binding proteins), which mediate the regulatory functions of lipid metabolism. Transcription factors HNF4-α (Hepatocyte nuclear factor 4), c-Myc, SP1 (Sp1 transcription factor), ESR1 (estrogen receptor 1, nuclear), and androgen receptor, along with several others, were centered as the hubs of transcription regulation networks. The data also provided direct evidence that α-tocopherol is involved in maintaining immuno-homeostasis through targeting the C3 (Complement Component 3) gene.

本研究通过对α-生育酚诱导的牛细胞基因扰动的全局表达谱和通路分析,对α-生育酚的生理功能有了全面的了解。数据证实α-生育酚是基因表达的有效调节剂,α-生育酚具有影响重要生物过程的新型转录活性。所鉴定的基因属于广泛的功能类别,并为其独特的作用提供了分子基础。基因调控网络富集分析表明,α-生育酚可改变脂质代谢的典型途径和介导脂质代谢调控功能的转录因子SREBP1和SREBP2。转录因子HNF4-α(肝细胞核因子4),c-Myc, SP1 (SP1转录因子),ESR1(雌激素受体1,核)和雄激素受体,以及其他几个转录调控网络的中心。这些数据也提供了α-生育酚通过靶向C3(补体成分3)基因参与维持免疫稳态的直接证据。
{"title":"Alpha-Tocopherol Modulates Transcriptional Activities that Affect Essential Biological Processes in Bovine Cells.","authors":"Cong-Jun Li,&nbsp;Robert W Li,&nbsp;Theodore H Elsasser","doi":"10.4137/GRSB.S6007","DOIUrl":"https://doi.org/10.4137/GRSB.S6007","url":null,"abstract":"<p><p>Using global expression profiling and pathway analysis on α-tocopherol-induced gene perturbation in bovine cells, this study has generated comprehensive information on the physiological functions of α-tocopherol. The data confirmed α-tocopherol is a potent regulator of gene expression and α-tocopherol possesses novel transcriptional activities that affect essential biological processes. The genes identified fall within a broad range of functional categories and provide the molecular basis for its distinctive effects. Enrichment analyses of gene regulatory networks indicate α-tocopherol alter the canonical pathway of lipid metabolism and transcription factors SREBP1 and SREBP2, (Sterol regulatory element binding proteins), which mediate the regulatory functions of lipid metabolism. Transcription factors HNF4-α (Hepatocyte nuclear factor 4), c-Myc, SP1 (Sp1 transcription factor), ESR1 (estrogen receptor 1, nuclear), and androgen receptor, along with several others, were centered as the hubs of transcription regulation networks. The data also provided direct evidence that α-tocopherol is involved in maintaining immuno-homeostasis through targeting the C3 (Complement Component 3) gene.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"109-24"},"PeriodicalIF":0.0,"publicationDate":"2010-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S6007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29535086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Overexpression of Colligin 2 in Glioma Vasculature is Associated with Overexpression of Heat Shock Factor 2. 胶质瘤血管中胶原蛋白2的过度表达与热休克因子2的过度表达有关。
Pub Date : 2010-10-20 DOI: 10.4137/GRSB.S4546
Dana A M Mustafa, Anieta M Sieuwerts, Ping Pin Zheng, Johan M Kros

In previous studies we found expression of the protein colligin 2 (heat shock protein 47 (HSP47), SERPINH1) in glioma neovasculature while not in normal brain tissue. Generally, the regulation of heat shock gene expression in eukaryotes is mediated by heat shock factors (HSF). In mammals, three heat shock transcription factors, HSF-1, -2, and -4, have been isolated. Here we investigated the relation between the expression of colligin 2 and these heat shock factors at the mRNA level using real-time reverse transcriptase PCR (qRT-PCR) in different grades of astrocytic tumorigenesis, viz., low-grade glioma and glioblastoma. Endometrium samples, representing physiological angiogenesis, were included as controls. Since colligin 2 is a chaperon for collagens, the gene expression of collagen I (COL1A1) was also investigated. The blood vessel density of the samples was monitored by expression of the endothelial marker CD31 (PECAM1). Because NG2-immunopositive pericytic cells are involved in glioma neovascularization, the expression of NG2 (CSPG4) was also measured.We demonstrate overexpression of HSF2 in both stages of glial tumorigenesis (reaching significance only in low-grade glioma) and also minor elevated levels of HSF1 as compared to normal brain. There were no differences in expression of HSF4 between low-grade glioma and normal brain while HSF4 was downregulated in glioblastoma. In the endometrium samples, none of the HSFs were upregulated. In the low-grade gliomas SERPINH appeared to be slightly overexpressed with a parallel 4-fold upregulation of COL1A1, while in glioblastoma there was over 5-fold overexpression of SERPINH1 and more than 150-fold overexpression of COL1A1. In both the lowgrade gliomas and the glioblastomas overexpression of CSPG4 was found and overexpression of PECAM1 was only found in the latter. Our data suggest that the upregulated expression of colligin 2 in glioma is accompanied by upregulation of COL1A1, CSPG4, HSF2 and to a lesser extent, HSF1. Further studies will unravel the association of these factors with colligin 2 expression, possibly leading to keys for therapeutic intervention.

在之前的研究中,我们发现胶原蛋白2(热休克蛋白47 (HSP47), SERPINH1)在胶质瘤新生血管中表达,而在正常脑组织中不表达。一般来说,真核生物热休克基因表达的调控是由热休克因子(heat shock factors, HSF)介导的。在哺乳动物中,已经分离出三种热休克转录因子HSF-1、-2和-4。本研究采用实时逆转录酶PCR (real-time reverse transcriptase PCR, qRT-PCR)技术,在不同级别的星形细胞瘤,即低级别胶质瘤和胶质母细胞瘤中,研究了胶原蛋白2的表达与这些热休克因子在mRNA水平上的关系。代表生理性血管生成的子宫内膜样本作为对照。由于胶原蛋白2是胶原蛋白的伴侣蛋白,我们也研究了胶原蛋白I (COL1A1)的基因表达。通过内皮标志物CD31 (PECAM1)的表达监测样本的血管密度。由于NG2免疫阳性的周细胞参与了胶质瘤新生血管的形成,我们也测量了NG2 (CSPG4)的表达。我们发现HSF2在胶质瘤发生的两个阶段都过表达(仅在低级别胶质瘤中达到显著性),并且与正常大脑相比,HSF2水平也有轻微升高。HSF4在低级别脑胶质瘤和正常脑中表达无差异,而在胶质母细胞瘤中表达下调。在子宫内膜样本中,hsf均未上调。在低级别胶质瘤中,SERPINH出现轻微过表达,COL1A1平行上调4倍,而在胶质母细胞瘤中,SERPINH1过表达超过5倍,COL1A1过表达超过150倍。在低级别胶质瘤和胶质母细胞瘤中均发现CSPG4过表达,而PECAM1仅在后者中过表达。我们的数据表明,胶质瘤中胶原蛋白2的表达上调伴随着COL1A1、CSPG4、HSF2以及HSF1的表达上调。进一步的研究将揭示这些因子与胶原蛋白2表达的关系,可能为治疗干预提供关键。
{"title":"Overexpression of Colligin 2 in Glioma Vasculature is Associated with Overexpression of Heat Shock Factor 2.","authors":"Dana A M Mustafa,&nbsp;Anieta M Sieuwerts,&nbsp;Ping Pin Zheng,&nbsp;Johan M Kros","doi":"10.4137/GRSB.S4546","DOIUrl":"https://doi.org/10.4137/GRSB.S4546","url":null,"abstract":"<p><p>In previous studies we found expression of the protein colligin 2 (heat shock protein 47 (HSP47), SERPINH1) in glioma neovasculature while not in normal brain tissue. Generally, the regulation of heat shock gene expression in eukaryotes is mediated by heat shock factors (HSF). In mammals, three heat shock transcription factors, HSF-1, -2, and -4, have been isolated. Here we investigated the relation between the expression of colligin 2 and these heat shock factors at the mRNA level using real-time reverse transcriptase PCR (qRT-PCR) in different grades of astrocytic tumorigenesis, viz., low-grade glioma and glioblastoma. Endometrium samples, representing physiological angiogenesis, were included as controls. Since colligin 2 is a chaperon for collagens, the gene expression of collagen I (COL1A1) was also investigated. The blood vessel density of the samples was monitored by expression of the endothelial marker CD31 (PECAM1). Because NG2-immunopositive pericytic cells are involved in glioma neovascularization, the expression of NG2 (CSPG4) was also measured.We demonstrate overexpression of HSF2 in both stages of glial tumorigenesis (reaching significance only in low-grade glioma) and also minor elevated levels of HSF1 as compared to normal brain. There were no differences in expression of HSF4 between low-grade glioma and normal brain while HSF4 was downregulated in glioblastoma. In the endometrium samples, none of the HSFs were upregulated. In the low-grade gliomas SERPINH appeared to be slightly overexpressed with a parallel 4-fold upregulation of COL1A1, while in glioblastoma there was over 5-fold overexpression of SERPINH1 and more than 150-fold overexpression of COL1A1. In both the lowgrade gliomas and the glioblastomas overexpression of CSPG4 was found and overexpression of PECAM1 was only found in the latter. Our data suggest that the upregulated expression of colligin 2 in glioma is accompanied by upregulation of COL1A1, CSPG4, HSF2 and to a lesser extent, HSF1. Further studies will unravel the association of these factors with colligin 2 expression, possibly leading to keys for therapeutic intervention.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"103-7"},"PeriodicalIF":0.0,"publicationDate":"2010-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S4546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29465401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Omega-6 fat supplementation alters lipogenic gene expression in bovine subcutaneous adipose tissue. 补充Omega-6脂肪可改变牛皮下脂肪组织中脂肪生成基因的表达。
Pub Date : 2010-10-19 DOI: 10.4137/GRSB.S5831
Sandeep J Joseph, Scott L Pratt, Enrique Pavan, Romdhane Rekaya, Susan K Duckett

In contrast to rodents, adipose tissue serves as the major site of lipogenesis and storage reservoir for excess dietary energy in cattle. Research in rodents shows that adding corn oil (57% C18:2 n-6) to the diet alters lipogenesis enhancing deposition of omega-6 fatty acids. This study examines changes in lipogenic gene expression of subcutaneous adipose tissue from eighteen steers fed increasing levels of dietary corn oil [0 (NONE), 0.31 kg/d (MED) and 0.62 kg/d (HI)] using two platforms, qPCR and microarray. The results show that MED level of oil supplementation up-regulates gene expression of key lipogenic enzymes but that as oil supplementation reaches HI level mRNA encoding lipogenic enzymes responsible for de novo synthesis and desaturation are down-regulated. Changes in specific lipogenic mRNA levels are correlated with changes in tissue fatty acid composition where de novo and desatured fatty acids were reduced with the highest level of oil supplementation.

与啮齿类动物不同,牛的脂肪组织是脂肪生成的主要部位,也是多余膳食能量的储存库。对啮齿动物的研究表明,在饮食中添加玉米油(57% C18:2 n-6)可以改变脂肪生成,促进-6脂肪酸的沉积。本研究采用qPCR和微阵列两种平台,研究了饲喂不同玉米油水平(0 (NONE)、0.31 kg/d (MED)和0.62 kg/d (HI))的18头肉牛皮下脂肪组织脂质基因表达的变化。结果表明,添加油的MED水平上调了关键脂肪生成酶的基因表达,而当添加油达到HI水平时,负责从头合成和去饱和的脂肪生成酶的mRNA编码下调。特定脂肪生成mRNA水平的变化与组织脂肪酸组成的变化相关,其中最高水平的油补充减少了新生脂肪酸和不饱和脂肪酸。
{"title":"Omega-6 fat supplementation alters lipogenic gene expression in bovine subcutaneous adipose tissue.","authors":"Sandeep J Joseph,&nbsp;Scott L Pratt,&nbsp;Enrique Pavan,&nbsp;Romdhane Rekaya,&nbsp;Susan K Duckett","doi":"10.4137/GRSB.S5831","DOIUrl":"https://doi.org/10.4137/GRSB.S5831","url":null,"abstract":"<p><p>In contrast to rodents, adipose tissue serves as the major site of lipogenesis and storage reservoir for excess dietary energy in cattle. Research in rodents shows that adding corn oil (57% C18:2 n-6) to the diet alters lipogenesis enhancing deposition of omega-6 fatty acids. This study examines changes in lipogenic gene expression of subcutaneous adipose tissue from eighteen steers fed increasing levels of dietary corn oil [0 (NONE), 0.31 kg/d (MED) and 0.62 kg/d (HI)] using two platforms, qPCR and microarray. The results show that MED level of oil supplementation up-regulates gene expression of key lipogenic enzymes but that as oil supplementation reaches HI level mRNA encoding lipogenic enzymes responsible for de novo synthesis and desaturation are down-regulated. Changes in specific lipogenic mRNA levels are correlated with changes in tissue fatty acid composition where de novo and desatured fatty acids were reduced with the highest level of oil supplementation.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"91-101"},"PeriodicalIF":0.0,"publicationDate":"2010-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S5831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29465402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
期刊
Gene regulation and systems biology
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