Histone H3 lysine 4 monomethylation modulates long-range chromatin interactions at enhancers.
Histone H3 lysine 4 monomethylation modulates long-range chromatin interactions at enhancers.
复制标题
组蛋白 H3 赖氨酸 4 单甲基化调节增强子处的长程染色质相互作用。
DOI：
10.1038/cr.2018.18
复制
发表时间：
2018
期刊：
影响因子：
44.1
通讯作者：
Ren,Bing
中科院分区：
文献类型：
--
作者：
Yan,Jian;Chen,Shi-AnA;Local,Andrea;Liu,Tristin;Qiu,Yunjiang;Dorighi,KristelM;Preissl,Sebastian;Rivera,ChloeM;Wang,Chaochen;Ye,Zhen;Ge,Kai;Hu,Ming;Wysocka,Joanna;Ren,Bing
增强子和启动子之间的远程染色质相互作用对于哺乳动物和其他后生动物中许多发育控制基因的转录至关重要。目前，将远端增强子连接到其特异性靶启动子的确切机制仍有待充分阐明。在这里，我们表明，增强子特异性组蛋白H3赖氨酸4单甲基化（H3 K4 me 1）和组蛋白甲基转移酶MLL 3和MLL 4（MLL 3/4）在这一过程中发挥了积极的作用。我们证明，在分化小鼠胚胎干细胞，MLL 3/4-依赖沉积的H3 K4 me 1在增强子与染色质相互作用的水平增加，而这种组蛋白修饰的损失导致染色质相互作用的水平降低和缺陷的基因激活在分化过程中。H3 K4 me 1在体外和体内促进了粘着蛋白复合物（一种已知的染色质组织调节剂）向染色质的募集，为MLL 3/4促进增强子和启动子之间的染色质相互作用提供了潜在的机制。总之，我们的研究结果支持MLL 3/4依赖性H3 K4 me 1在哺乳动物细胞增强子处协调长距离染色质相互作用的作用。
Long-range chromatin interactions between enhancers and promoters are essential for transcription of many developmentally controlled genes in mammals and other metazoans. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here, we show that the enhancer-specific histone H3 lysine 4 monomethylation (H3K4me1) and the histone methyltransferases MLL3 and MLL4 (MLL3/4) play an active role in this process. We demonstrate that in differentiating mouse embryonic stem cells, MLL3/4-dependent deposition of H3K4me1 at enhancers correlates with increased levels of chromatin interactions, whereas loss of this histone modification leads to reduced levels of chromatin interactions and defects in gene activation during differentiation. H3K4me1 facilitates recruitment of the Cohesin complex, a known regulator of chromatin organization, to chromatin in vitro and in vivo, providing a potential mechanism for MLL3/4 to promote chromatin interactions between enhancers and promoters. Taken together, our results support a role for MLL3/4-dependent H3K4me1 in orchestrating long-range chromatin interactions at enhancers in mammalian cells.