Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China, VYM Genome Research Center, National Yang-Ming University, University System of Taiwan, Taipei 11221, Taiwan, Republic of China and Chien-Tien Hsu Cancer Research Foundation, Taipei 11221, Taiwan, Republic of China.
Nucleic Acids Res. 2014 Mar;42(5):3073-88. doi: 10.1093/nar/gkt1341. Epub 2013 Dec 25.
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.
在 MCF-7 细胞和雌激素受体阳性的临床乳腺癌组织中，依赖复制的组蛋白 H2A 同工型 H2ac 上调。这种 H2A 同工型的细胞耗竭导致雌激素信号转导缺陷、细胞增殖丧失和细胞周期停滞在 G0/G1 期。H2ac 通过其 HAR 结构域募集雌激素受体 α，介导雌激素受体靶基因（特别是 BCL2 和 c-MYC）的调节，并促进相应基因的启动子、增强子和 3'-非翻译区之间染色质环的形成。这些发现揭示了组蛋白同工型在癌细胞基因表达调控中的新作用，并表明这些分子可能成为抗癌药物发现的靶点。
