Towards resolving the transcription factor network controlling myelin gene expression.
Towards resolving the transcription factor network controlling myelin gene expression.
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DOI：
10.1093/nar/gkr326
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发表时间：
2011-10
影响因子：
14.9
通讯作者：
Peterson AC
中科院分区：
文献类型：
--
作者：
Fulton DL;Denarier E;Friedman HC;Wasserman WW;Peterson AC
在中枢神经系统（CNS）中，髓磷脂由螺旋缠绕的少突胶质细胞质膜产生，并且如在诸如多发性硬化症的疾病中的遗传性或获得性髓磷脂异常的衰弱效应所例示的，髓磷脂在神经系统功能中起关键作用。髓鞘的产生与许多基因的快速上调相一致。它们随后表达模式的复杂性，沿着最近认识到的少突胶质细胞谱系内的异质性，表明控制这些基因的调控网络驱动多个上下文特异性转录程序。赋予这种微妙的控制水平可能涉及大量相互作用的转录因子（TF）。在这里，我们结合新的策略，计算序列分析与体内功能分析，建立协调髓鞘相关基因转录的TF网络模型。值得注意的是，该网络模型捕获了已知调节少突胶质细胞髓鞘基因转录和/或少突胶质细胞发育的调控DNA元件和TF，从而验证了我们的方法。此外，它链接到许多以前未知的作用在中枢神经系统髓鞘形成的TF，并建议之间的合作关系，已知的和新的TF，从而提供了更深入的了解髓鞘基因转录网络。
In the central nervous system (CNS), myelin is produced from spirally-wrapped oligodendrocyte plasma membrane and, as exemplified by the debilitating effects of inherited or acquired myelin abnormalities in diseases such as multiple sclerosis, it plays a critical role in nervous system function. Myelin sheath production coincides with rapid up-regulation of numerous genes. The complexity of their subsequent expression patterns, along with recently recognized heterogeneity within the oligodendrocyte lineage, suggest that the regulatory networks controlling such genes drive multiple context-specific transcriptional programs. Conferring this nuanced level of control likely involves a large repertoire of interacting transcription factors (TFs). Here, we combined novel strategies of computational sequence analyses with in vivo functional analysis to establish a TF network model of coordinate myelin-associated gene transcription. Notably, the network model captures regulatory DNA elements and TFs known to regulate oligodendrocyte myelin gene transcription and/or oligodendrocyte development, thereby validating our approach. Further, it links to numerous TFs with previously unsuspected roles in CNS myelination and suggests collaborative relationships amongst both known and novel TFs, thus providing deeper insight into the myelin gene transcriptional network.
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影响因子：
14.9
作者：
Blanco E;Farré D;Albà MM;Messeguer X;Guigó R
通讯作者：
Guigó R
影响因子：
3.7
作者：
Chen CT;Gottlieb DI;Cohen BA
通讯作者：
Cohen BA
DOI：
10.1073/pnas.93.17.9067
发表时间：
1996-08-20
影响因子：
11.1
作者：
Bronson, SK;Plaehn, EG;Smithies, O
通讯作者：
Smithies, O
DOI：
10.1073/pnas.0609184103
发表时间：
2006-12-19
影响因子：
11.1
作者：
Alcaraz, Wendy A.;Gold, David A.;Hamilton, Bruce A.
通讯作者：
Hamilton, Bruce A.
影响因子：
14.9
作者：
Barrett T;Troup DB;Wilhite SE;Ledoux P;Rudnev D;Evangelista C;Kim IF;Soboleva A;Tomashevsky M;Marshall KA;Phillippy KH;Sherman PM;Muertter RN;Edgar R
通讯作者：
Edgar R