G9a/GLP-sensitivity of H3K9me2 Demarcates Two Types of Genomic Compartments |
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| Authors: | Zixiang Yan Luzhang Ji Xiangru Huo Qianfeng Wang Yuwen Zhang Bo Wen |
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| Affiliation: | 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 |
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| Abstract: | 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. |
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| Keywords: | H3K9me2 G9a/GLP Chromatin organization 3D genome Genomic compartment |
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