The role of master regulators in gene regulatory networks

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
E. Hern'andez-Lemus, K. Baca-L'opez, R. Lemus, R. Garc'ia-Herrera
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引用次数: 2

Abstract

Gene regulatory networks present a wide variety of dynamical responses to intrinsic and extrinsic perturbations. Arguably, one of the most important of such coordinated responses is the one of amplification cascades, in which activation of a few key-responsive transcription factors (termed master regulators, MRs) lead to a large series of transcriptional activation events. This is so since master regulators are transcription factors controlling the expression of other transcription factor molecules and so on. MRs hold a central position related to transcriptional dynamics and control of gene regulatory networks and are often involved in complex feedback and feedforward loops inducing non-trivial dynamics. Recent studies have pointed out to the myocyte enhancing factor 2C (MEF2C, also known as MADS box transcription enhancer factor 2, polypeptide C) as being one of such master regulators involved in the pathogenesis of primary breast cancer. In this work, we perform an integrative genomic analysis of the transcriptional regulation activity of MEF2C and its target genes to evaluate to what extent are these molecules inducing collective responses leading to gene expression deregulation and carcinogenesis. We also analyzed a number of induced dynamic responses, in particular those associated with transcriptional bursts, and nonlinear cascading to evaluate the influence they may have in malignant phenotypes and cancer. Received: 20 Novembre 2014,  Accepted: 24 June 2015;  Edited by: C. A. Condat, G. J. Sibona;  DOI: http://dx.doi.org/10.4279/PIP.070011 Cite as: E Hernandez-Lemus, K Baca-Lopez, R Lemus, R Garcia-Herrera, Papers in Physics 7, 070011 (2015) This paper, by E Hernandez-Lemus, K Baca-Lopez, R Lemus, R Garcia-Herrera , is licensed under the Creative Commons Attribution License 3.0 .
基因调控网络中主调控者的角色
基因调控网络对内在和外在扰动呈现出各种各样的动态响应。可以说,这种协调反应中最重要的一个是扩增级联反应,其中几个关键响应转录因子(称为主调控因子,MRs)的激活导致大量的转录激活事件。这是因为主调控因子是控制其他转录因子分子表达的转录因子等等。MRs在转录动力学和基因调控网络的控制中占据中心位置,经常参与复杂的反馈和前馈循环,诱导非平凡的动力学。近年来的研究指出,肌细胞增强因子2C (MEF2C,也称为MADS盒转录增强因子2,多肽C)是参与原发性乳腺癌发病机制的主要调控因子之一。在这项工作中,我们对MEF2C及其靶基因的转录调控活性进行了综合基因组分析,以评估这些分子在多大程度上诱导集体反应,导致基因表达失调和致癌。我们还分析了一些诱导的动态反应,特别是那些与转录爆发和非线性级联相关的反应,以评估它们在恶性表型和癌症中可能产生的影响。收稿日期:2014年11月20日,收稿日期:2015年6月24日;编辑:C. A. Condat, G. J. Sibona;E Hernandez-Lemus, K Baca-Lopez, R Lemus, R Garcia-Herrera, Papers in Physics 7,070011(2015)本文由E Hernandez-Lemus, K Baca-Lopez, R Lemus, R Garcia-Herrera根据知识共享署名许可3.0授权。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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