California Institute for Quantitative Biosciences (QB3) , University of California , Berkeley , California 94720 , United States.
Molecular Biophysics and Integrated Bioimaging Division , Lawrence Berkeley National Laboratory , Berkeley , California 94720 , United States.
Biochemistry. 2019 Feb 5;58(5):346-354. doi: 10.1021/acs.biochem.8b01064. Epub 2018 Dec 3.
Polycomb group proteins are transcriptional repressors controlling gene expression patterns and maintaining cell type identity. The chemical modifications of histones and DNA caused by the regulated activity of chromatin-modifying enzymes such as Polycomb help establish and maintain such expression patterns. Polycomb repressive complex 2 (PRC2) is the only known methyltransferase specific for histone H3 lysine 27 (H3K27) and catalyzes its trimethylation leading to the repressive H3K27me3 mark. Structural biology has made important contributions to our understanding of the molecular mechanisms that ensure the spatiotemporal regulation of PRC2 activity and the establishment of inactive chromatin domains marked by H3K27me3. In this review, we discuss the recent structural studies that have advanced our understanding of PRC2 function, in particular the roles of intersubunit interactions in complex assembly and the regulation of methyltransferase activity, as well as the mechanism of local H3K27me3 spreading leading to repressive domains.
多梳蛋白是转录抑制因子，控制基因表达模式并维持细胞类型的特征。染色质修饰酶（如 Polycomb）的调节活性引起的组蛋白和 DNA 的化学修饰有助于建立和维持这种表达模式。多梳抑制复合物 2（PRC2）是唯一已知的特异性组蛋白 H3 赖氨酸 27（H3K27）甲基转移酶，催化其三甲基化，导致抑制性 H3K27me3 标记。结构生物学为我们理解确保 PRC2 活性的时空调节和由 H3K27me3 标记的无活性染色质域的建立的分子机制做出了重要贡献。在这篇综述中，我们讨论了最近的结构研究，这些研究增进了我们对 PRC2 功能的理解，特别是亚基间相互作用在复合物组装和甲基转移酶活性调节中的作用，以及导致抑制性域的局部 H3K27me3 扩散的机制。
