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 ...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(H3 K9 me2), one of the abundant histone modifications, in three-dimensional(3 D)genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9 a and GLP in differentiated cells eliminated H3 K9 me2 predominantly at A-type(active) genomic compartments, and the level of residual H3 K9 me2 modifications was strongly associated with B-type(inactive) genomic compartments. Furthermore, chemical inhibition of G9 a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9 a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3 D chromatin. Collectively, our data demonstrated essential roles of H3 K9 me2 in 3 D genome organization.展开更多
基金supported by the National Key R&D Program of China(Grant No.2018YFC1003500 awarded to BW)the National Natural Science Foundation of China(Grant No.31771435 awarded to BW)
文摘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(H3 K9 me2), one of the abundant histone modifications, in three-dimensional(3 D)genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9 a and GLP in differentiated cells eliminated H3 K9 me2 predominantly at A-type(active) genomic compartments, and the level of residual H3 K9 me2 modifications was strongly associated with B-type(inactive) genomic compartments. Furthermore, chemical inhibition of G9 a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9 a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3 D chromatin. Collectively, our data demonstrated essential roles of H3 K9 me2 in 3 D genome organization.
