An H2A histone isotype regulates estrogen receptor target genes by mediating enhancer-promoter-3 %26apos;-UTR interactions in breast cancer cells

作者：Su Chia Hsin; Tzeng Tsai Yu; Cheng Ching; Hsu Ming Ta^*

来源：Nucleic Acids Research, 2014, 42(5): 3073-3088.

DOI：10.1093/nar/gkt1341

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%26apos;-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.

• 出版日期2014-3