van Kruijsbergen Ila, Hontelez Saartje, Veenstra Gert Jan C
Radboud University Nijmegen, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen 6500 HB, The Netherlands.
Radboud University Nijmegen, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen 6500 HB, The Netherlands.
Int J Biochem Cell Biol. 2015 Oct;67:177-87. doi: 10.1016/j.biocel.2015.05.006. Epub 2015 May 14.
Polycomb group (PcG) proteins are key regulators in establishing a transcriptional repressive state. Polycomb Repressive Complex 2 (PRC2), one of the two major PcG protein complexes, is essential for proper differentiation and maintenance of cellular identity. Multiple factors are involved in recruiting PRC2 to its genomic targets. In this review, we will discuss the role of DNA sequence, transcription factors, pre-existing histone modifications, and RNA in guiding PRC2 towards specific genomic loci. The DNA sequence itself influences the DNA methylation state, which is an important determinant of PRC2 recruitment. Other histone modifications are also important for PRC2 binding as PRC2 can respond to different cellular states via crosstalk between histone modifications. Additionally, PRC2 might be able to sense the transcriptional status of genes by binding to nascent RNA, which could also guide the complex to chromatin. In this review, we will discuss how all these molecular aspects define a local chromatin state which controls accurate, cell-type-specific epigenetic silencing by PRC2. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.
多梳蛋白家族（PcG）蛋白是建立转录抑制状态的关键调节因子。多梳抑制复合物2（PRC2）是两种主要的PcG蛋白复合物之一，对于细胞的正常分化和细胞身份的维持至关重要。多种因素参与将PRC2招募到其基因组靶点。在这篇综述中，我们将讨论DNA序列、转录因子、预先存在的组蛋白修饰和RNA在引导PRC2靶向特定基因组位点中的作用。DNA序列本身会影响DNA甲基化状态，而DNA甲基化状态是PRC2招募的一个重要决定因素。其他组蛋白修饰对于PRC2的结合也很重要，因为PRC2可以通过组蛋白修饰之间的串扰对不同的细胞状态做出反应。此外，PRC2可能能够通过与新生RNA结合来感知基因的转录状态，这也可能将该复合物导向染色质。在这篇综述中，我们将讨论所有这些分子层面如何定义一种局部染色质状态，该状态通过PRC2控制精确的、细胞类型特异性的表观遗传沉默。本文是名为“发育和疾病中的表观遗传学动态”的定向专题的一部分。
