Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY 10016, USA.
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Mol Cell. 2014 Mar 20;53(6):979-92. doi: 10.1016/j.molcel.2014.02.032.
Monomethylation of lysine 4 on histone H3 (H3K4me1) is a well-established feature of enhancers and promoters, although its function is unknown. Here, we uncover roles for H3K4me1 in diverse cell types. Remarkably, we find that MLL3/4 provokes monomethylation 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. Monomethylation-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 embryonic stem cells (ESCs). 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 monomethylation in establishing boundaries that restrict the recruitment of chromatin-modifying enzymes to defined regions within promoters.
组蛋白 H3 赖氨酸 4 的单甲基化（H3K4me1）是增强子和启动子的一个公认特征，尽管其功能尚不清楚。在这里，我们揭示了 H3K4me1 在多种细胞类型中的作用。值得注意的是，我们发现 MLL3/4 促使启动子区域的单甲基化，并在成肌细胞中条件性抑制肌肉和炎症反应基因。在成肌过程中，肌肉基因被激活，失去 MLL3 占据，并通过替代 COMPASS 复合物被 H3K4 三甲基化。单甲基化介导的抑制作用不仅限于骨骼肌。与 H3K27me3 和 H4K20me1 一起，H3K4me1 与胚胎成纤维细胞、巨噬细胞和人类胚胎干细胞（ESC）中的转录沉默有关。在活性基因的启动子上，我们发现 H3K4me1 空间上划定了与 H3K4me3 相互作用的因子的招募，包括 ING1，它反过来又招募 Sin3A。我们的发现指出了 H3K4 单甲基化在建立边界方面的独特作用，该边界限制了染色质修饰酶在启动子内特定区域的招募。
