Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka, 812-0054, Japan.
Graduate School of Biomedical Science, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Nat Commun. 2018 Apr 11;9(1):1400. doi: 10.1038/s41467-018-03845-1.
Regulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule. Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable H3mm7 nucleosome may be required for proper skeletal muscle differentiation.
基因表达的调控需要组蛋白 H3 变体 H3.3 选择性地掺入染色质。组蛋白 H3.3 有几个亚变体，但它们的功能尚不清楚。在这里，我们描述了组蛋白 H3.3 亚变体 H3mm7 的功能，它在骨骼肌卫星细胞中表达。H3mm7 敲除小鼠表明 H3mm7 在骨骼肌再生中具有重要作用。染色质分析显示，H3mm7 通过在启动子区域形成开放染色质结构，包括肌生成基因的启动子区域，从而促进转录。包含 H3mm7 的核小体的晶体结构表明，与其他 H3 蛋白的 S57 残基不同，H3mm7 特有的 A57 残基不能与同源 H4 分子的 R40 残基形成氢键。因此，与 H3.3 核小体相比，H3mm7 核小体在体外不稳定，在体内具有更高的迁移率。我们得出结论，不稳定的 H3mm7 核小体可能是骨骼肌分化所必需的。
