MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China.
Genomics Proteomics Bioinformatics. 2020 Aug;18(4):359-370. doi: 10.1016/j.gpb.2020.08.001. Epub 2020 Dec 5.
In the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these architectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modifications was strongly associated with B-type (inactive) genomic compartments. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.
在核内，染色质折叠成层次结构，与各种核功能紧密相关。然而，赋予这些结构的潜在分子机制仍不完全清楚。在这里，我们研究了 H3 赖氨酸 9 二甲基化（H3K9me2）作为丰富的组蛋白修饰之一在三维（3D）基因组组织中的功能作用。与在小鼠胚胎干细胞中不同，在分化细胞中抑制甲基转移酶 G9a 和 GLP 主要消除 A 型（活性）基因组区室中的 H3K9me2，而残留的 H3K9me2 修饰水平与 B 型（非活性）基因组区室强烈相关。此外，在小鼠肝细胞中化学抑制 G9a/GLP 主要导致 G9a/GLP 敏感区域的染色质-核层相互作用减少，基因组区室化程度增加，以及数百个与 3D 染色质改变相关的基因上调。总的来说，我们的数据表明 H3K9me2 在 3D 基因组组织中具有重要作用。
