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.

在细胞核中，染色质折叠成与各种核功能紧密相连的分层结构。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 )（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。与小鼠胚胎干细胞不同，分化细胞中甲基转移酶 G9a 和 GLP 的抑制主要消除了 A 型（活性）基因组区室中的 H3K9me2 ，并且残留 H3K9me2 修饰的水平与 B 型（非活性）基因组区室密切相关。此外，小鼠肝细胞中G9a/GLP的化学抑制导致主要在 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，以及与 3D 改变相关的数百个基因上调。染色质。总的来说，我们的数据证明了 H3K9me2 在3D 基因组组织中的重要作用。