Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put.
Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put.
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DOI：
10.1016/j.molcel.2013.02.013
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发表时间：
2013-03-07
期刊：
影响因子：
16
通讯作者：
Kingston, Robert E.
中科院分区：
文献类型：
--
作者：
Simon, Jeffrey A.;Kingston, Robert E.
多梳抑制复合物是保守的染色质调节因子，在多细胞发育、干细胞生物学和癌症中具有关键作用。新的发现推进了对它们如何靶向作用位点的分子理解，与局部染色质相互作用并改变局部染色质以沉默基因，并在连续几代增殖细胞中保持沉默。Polycomb蛋白对染色质的修饰为高等真核生物的基因沉默提供了一种重要的策略。多梳抑制复合物（PRCs）沉默许多关键的发育调节因子，并集中整合在胚胎和成体干细胞的转录回路。PRC 2使赖氨酸-27（H3-K27 me 3）上的组蛋白H3三甲基化，PRC 1型复合物使组蛋白H2 A和紧凑的多核小体泛素化。PRCs和这些特征活动如何被部署以选择和沉默基因组靶标是当前激烈研究的主题。我们回顾了PRC 1和PRC 2的靶向、调节和功能方面的最新进展，并考虑了在Polycomb沉默中影响转录步骤的定义方面的进展。最近的关键发现表明PRC 1靶向独立于H3-K27 me 3，并强调非酶PRC 1介导的压缩。我们还评估了Polycomb机器和非编码RNA之间的扩展连接。令人兴奋的新研究提供了第一个系统的分析发生了什么多梳复合物，相关的组蛋白修饰，在大规模的染色质重组，伴随着DNA复制和有丝分裂。现在的阶段是揭示基本的表观遗传机制，决定如何Polycomb靶基因沉默，以及如何Polycomb沉默是通过细胞周期进程保存。
Polycomb repressive complexes are conserved chromatin regulators with key roles in multicellular development, stem cell biology, and cancer. New findings advance molecular understanding of how they target to sites of action, interact with and alter local chromatin to silence genes, and maintain silencing in successive generations of proliferating cells. Chromatin modification by Polycomb proteins provides an essential strategy for gene silencing in higher eukaryotes. Polycomb repressive complexes (PRCs) silence many key developmental regulators and are centrally integrated in the transcriptional circuitry of embryonic and adult stem cells. PRC2 trimethylates histone H3 on lysine-27 (H3-K27me3) and PRC1-type complexes ubiquitylate histone H2A and compact polynucleosomes. How PRCs and these signature activities are deployed to select and silence genomic targets is the subject of intense current investigation. We review recent advances on targeting, modulation, and functions of PRC1 and PRC2, and we consider progress on defining transcriptional steps impacted in Polycomb silencing. Key recent findings demonstrate PRC1 targeting independent of H3-K27me3 and emphasize nonenzymatic PRC1-mediated compaction. We also evaluate expanding connections between Polycomb machinery and non-coding RNAs. Exciting new studies supply the first systematic analyses of what happens to Polycomb complexes, and associated histone modifications, during the wholesale chromatin reorganizations that accompany DNA replication and mitosis. The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and how Polycomb silence is preserved through cell cycle progression.
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影响因子：
7.7
作者：
Ciferri C;Lander GC;Maiolica A;Herzog F;Aebersold R;Nogales E
通讯作者：
Nogales E
影响因子：
23.9
作者：
Brookes, Emily;de Santiago, Ines;Hebenstreit, Daniel;Morris, Kelly J.;Carroll, Tom;Xie, Sheila Q.;Stock, Julie K.;Heidemann, Martin;Eick, Dirk;Nozaki, Naohito;Kimura, Hiroshi;Ragoussis, Jiannis;Teichmann, Sarah A.;Pombo, Ana
通讯作者：
Pombo, Ana
影响因子：
7.8
作者：
Buchenau, P;Hodgson, J;Strutt, H;Arndt-Jovin, DJ
通讯作者：
Arndt-Jovin, DJ
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
DOI：
10.1073/pnas.1118678109
发表时间：
2012-05-01
影响因子：
11.1
作者：
Beh, Leslie Y.;Colwell, Lucy J.;Francis, Nicole J.
通讯作者：
Francis, Nicole J.