An H2A histone isotype regulates estrogen receptor target genes by mediating enhancer-promoter-3′-UTR interactions in breast cancer cells |
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| Authors: | Chia-Hsin Su Tsai-Yu Tzeng Ching Cheng Ming-Ta Hsu |
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| Institution: | 1.Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China, 2.VYM Genome Research Center, National Yang-Ming University, University System of Taiwan, Taipei 11221, Taiwan, Republic of China and 3.Chien-Tien Hsu Cancer Research Foundation, Taipei 11221, Taiwan, Republic of China |
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| Abstract: | A replication-dependent histone H2A isotype, H2ac, is upregulated in MCF-7 cells and in estrogen receptor-positive clinical breast cancer tissues. Cellular depletion of this H2A isotype leads to defective estrogen signaling, loss of cell proliferation and cell cycle arrest at G0/G1 phase. H2ac mediates regulation of estrogen receptor target genes, particularly BCL2 and c-MYC, by recruiting estrogen receptor alpha through its HAR domain and facilitating the formation of a chromatin loop between the promoter, enhancer and 3′-untranslated region of the respective genes. These findings reveal a new role for histone isotypes in the regulation of gene expression in cancer cells, and suggest that these molecules may be targeted for anti-cancer drug discovery. |
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