A role for H3K4 monomethylation in gene repression and partitioning of chromatin readers.
A role for H3K4 monomethylation in gene repression and partitioning of chromatin readers.
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DOI：
10.1016/j.molcel.2014.02.032
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发表时间：
2014-03-20
期刊：
影响因子：
16
通讯作者：
Dynlacht, Brian D.
中科院分区：
文献类型：
--
作者：
Cheng, Jemmie;Blum, Roy;Bowman, Christopher;Hu, Deqing;Shilatifard, Ali;Shen, Steven;Dynlacht, Brian D.
组蛋白H3（H3 K4 me 1）上赖氨酸4的单甲基化是增强子和启动子的公认特征，尽管其功能尚不清楚。在这里，我们揭示了H3 K4 me 1在不同细胞类型中的新作用。值得注意的是，我们发现MLL 3/4引起成肌细胞启动子区域的单甲基化和肌肉和炎症反应基因的条件性抑制。在肌生成过程中，肌肉基因被激活，失去MLL 3占用，并通过替代的COMPASS复合物变成H3 K4-三甲基化。单甲基化介导的抑制不限于骨骼肌。与H3 K27 me 3和H4 K20 me 1一起，H3 K4 me 1与胚胎成纤维细胞、巨噬细胞和人ES细胞中的转录沉默相关。在活性基因的启动子上，我们发现H3 K4 me 1在空间上划分了与H3 K4 me 3相互作用的因子的募集，包括ING 1，其反过来募集Sin 3A。我们的研究结果指出了H3 K4单甲基化在建立限制染色质修饰酶募集到启动子内定义区域的边界方面的独特作用。
Mono-methylation of lysine 4 on histone H3 (H3K4me1) is a well-established feature of enhancers and promoters, although its function is unknown. Here, we reveal novel roles for H3K4me1 in diverse cell types. Remarkably, we find that MLL3/4 provokes mono-methylation of promoter regions and the conditional repression of muscle and inflammatory response genes in myoblasts. During myogenesis, muscle genes are activated, lose MLL3 occupancy, and become H3K4-trimethylated through an alternative COMPASS complex. Mono-methylation mediated repression was not restricted to skeletal muscle. Together with H3K27me3 and H4K20me1, H3K4me1 was associated with transcriptional silencing in embryonic fibroblasts, macrophages, and human ES cells. On promoters of active genes, we find that H3K4me1 spatially demarcates the recruitment of factors that interact with H3K4me3, including ING1, which, in turn, recruits Sin3A. Our findings point to a unique role for H3K4 mono-methylation in establishing boundaries that restrict the recruitment of chromatin-modifying enzymes to defined regions within promoters.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
16
作者：
Milne, TA;Briggs, SD;Hess, JL
通讯作者：
Hess, JL
视网膜母细胞瘤抑制组蛋白H3赖氨酸27的蛋白质依赖性甲基化与不可逆的细胞周期出口有关。
影响因子：
7.8
作者：
Blais, Alexandre;van Oevelen, Chris J. C.;Margueron, Raphael;Acosta-Alvear, Diego;Dynlacht, Brian David
通讯作者：
Dynlacht, Brian David
影响因子：
64.5
作者：
Heredia JE;Mukundan L;Chen FM;Mueller AA;Deo RC;Locksley RM;Rando TA;Chawla A
通讯作者：
Chawla A