Corepressor Protein CDYL Functions as a Molecular Bridge between Polycomb Repressor Complex 2 and Repressive Chromatin Mark Trimethylated Histone Lysine 27*
Corepressor Protein CDYL Functions as a Molecular Bridge between Polycomb Repressor Complex 2 and Repressive Chromatin Mark Trimethylated Histone Lysine 27*
复制标题
DOI：
10.1074/jbc.m111.271064
复制
发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Yu Zhang;Xiaohan Yang;B. Gui;Guojia Xie;Di Zhang;Y. Shang;Jing Liang
中科院分区：
文献类型：
--
作者：
Yu Zhang;Xiaohan Yang;B. Gui;Guojia Xie;Di Zhang;Y. Shang;Jing Liang
背景：多梳抑制复合物2（PRC2）甲基化组蛋白H3的赖氨酸27。结果：CDYL直接与PRC2和三甲基化组蛋白H3赖氨酸27（H3K27me3）相互作用，并增强PRC2的甲基转移酶活性。结论：CDYL是PRC2和H3K27me3之间的分子桥梁。重要性：CDYL促进PRC2介导的H3K27me3染色质修饰，导致抑制靶基因表达的抑制性染色质状态。多梳族蛋白在参与各种病理生理过程的多个基因家族的转录调控中发挥重要作用。据信多梳抑制复合物2（PRC2）通过EED亚基靶向染色质以甲基化组蛋白H3赖氨酸27（H3K27），导致抑制基因表达的抑制性染色质状态。在这里，我们报告了含有染色体结构域的蛋白质CDYL特异性识别二甲基化和三甲基化的H3K27（H3K27me2和H3K27me3），并直接与PRC 2的催化亚基EZH2相互作用。我们表明，CDYL显着提高PRC2的甲基转移酶的活性，在体外对核糖体底物。通过ChIP测序对CDYL靶标的全基因组分析显示，CDYL和PRC2共有许多基因组靶标。CDYL是PRC2在其共同靶位点处的染色质靶向和最大酶活性所需的。我们的实验表明，CDYL作为PRC 2和抑制性染色质标记H3 K27 me3之间的分子桥梁，形成正反馈环，以促进H3 K27 me3修饰沿着染色质的建立和传播。
Background: Polycomb Repressive Complex 2 (PRC2) methylates histone H3 at lysine 27. Results: CDYL directly interacts with PRC2 and tri-methylated histone H3 lysine 27 (H3K27me3) and enhances the methyltransferase activity of PRC2. Conclusion: CDYL is a molecular bridge between PRC2 and H3K27me3. Significance: CDYL facilitates PRC2-mediated H3K27me3 modifications of the chromatin, leading to a repressive chromatin state that inhibits target gene expression. Polycomb group proteins play essential roles in transcriptional regulation of multiple gene families involved in various pathophysiological processes. It is believed that Polycomb Repressive Complex 2 (PRC2) is targeted to chromatin by the EED subunit to methylate histone H3 lysine 27 (H3K27), leading to a repressive chromatin state that inhibits gene expression. Here we report that the chromodomain-containing protein CDYL specifically recognizes di- and tri-methylated H3K27 (H3K27me2 and H3K27me3) and directly interacts with EZH2, the catalytic subunit of PRC2. We show that CDYL dramatically enhances the methyltransferase activity of PRC2 toward oligonucleosome substrates in vitro. Genome-wide analysis of CDYL targets by ChIP sequencing revealed that CDYL and PRC2 share a number of genomic targets. CDYL is required for chromatin targeting and maximal enzymatic activity of PRC2 at their common target sites. Our experiments indicate that CDYL functions as a molecular bridge between PRC2 and the repressive chromatin mark H3K27me3, forming a positive feedback loop to facilitate the establishment and propagation of H3K27me3 modifications along the chromatin.