Decoding transcriptional repressor complexes in the adult central nervous system.
Decoding transcriptional repressor complexes in the adult central nervous system.
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DOI：
10.1016/j.neuropharm.2013.12.024
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发表时间：
2014-05
影响因子：
4.7
通讯作者：
Monteggia LM
中科院分区：
文献类型：
--
作者：
Adachi M;Monteggia LM
细胞通过平衡转录激活和抑制来维持精确的基因表达。虽然许多工作都集中在阐明中枢神经系统（CNS）中的转录激活，但人们对转录抑制知之甚少。抑制基因表达的一种方法是启动转录因子与 DNA 的结合，然后招募辅助抑制蛋白和其他辅助蛋白，形成多蛋白抑制复合物。这些多蛋白阻遏复合物包括组蛋白修饰酶，可触发组蛋白乙酰化、甲基化和泛素化等过程，改变染色质结构以影响基因表达。在这些复合物中，转录阻遏蛋白本身不表现出重塑染色质结构的酶反应，而组蛋白修饰酶缺乏内在的 DNA 结合活性，但具有处理组蛋白翻译后修饰的能力。因此，转录抑制因子和组蛋白修饰酶之间的相互关联对于塑造染色质以有利于转录抑制和下调基因表达至关重要。此外，共阻遏物是基因抑制中不可或缺的组成部分，因为它们连接转录阻遏物和组蛋白修饰酶。在这篇综述中，我们将讨论这些阻遏复合物的一些主要成分在中枢神经系统中的作用，以及它们可能构成动物基本行为的细胞功能。
Cells maintain precise gene expression by balancing transcriptional activation and repression. While much work has focused on elucidating transcriptional activation in the central nervous system (CNS), little is known about transcriptional repression. One means to repress gene expression is to initiate binding of transcription factors to DNA, which then recruit co-repressors as well as other accessory proteins, forming a multi-protein repressor complex. These multi-protein repressor complexes include histone modifying enzymes that trigger processes such as histone acetylation, methylation, and ubiquitylation, altering chromatin structures to impact gene expression. Within these complexes transcriptional repressor proteins per se do not exhibit enzymatic reactions to remodel chromatin structure, whereas histone modifying enzymes lack intrinsic DNA binding activity but have an ability to process post-translational modifications on histones. Thus, the mutual association between transcriptional repressors and histone modifying enzymes is essential to sculpt chromatin to favor transcriptional repression and down regulate gene expression. Additionally, co-repressors are integral components in the context of gene repression as they bridge the association of transcriptional repressors and histone modifying enzymes. In this review, we will discuss the roles of some of the major components of these repressor complex in the CNS as well as their cellular functions that may underlie fundamental behavior in animals.
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DOI：
10.1523/jneurosci.0097-09.2009
发表时间：
2009-06-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Akhtar MW;Raingo J;Nelson ED;Montgomery RL;Olson EN;Kavalali ET;Monteggia LM
通讯作者：
Monteggia LM
影响因子：
4.6
作者：
Covey, Matthew V.;Streb, Jeffrey W.;Ballas, Nurit
通讯作者：
Ballas, Nurit
影响因子：
3.5
作者：
Deng, Vivianne;Matagne, Valerie;Ojeda, Sergio R.
通讯作者：
Ojeda, Sergio R.
影响因子：
3.5
作者：
Collins, AL;Levenson, JM;Zoghbi, HY
通讯作者：
Zoghbi, HY
DOI：
10.1073/pnas.96.17.9873
发表时间：
1999-08-17
影响因子：
11.1
作者：
Andrés, ME;Burger, C;Mandel, G
通讯作者：
Mandel, G