GATA4调节雌激素受体α介导的成骨细胞转录。
GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription.
作者信息
Miranda-Carboni Gustavo A, Guemes Miriam, Bailey Shannon, Anaya Edgar, Corselli Mirko, Peault Bruno, Krum Susan A
机构信息
Department of Obstetrics and Gynecology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
出版信息
Mol Endocrinol. 2011 Jul;25(7):1126-36. doi: 10.1210/me.2010-0463. Epub 2011 May 12.
Estrogens regulate osteoblast differentiation and mineralization. We identified GATA4 as a transcription factor expressed in osteoblasts and directly regulated by 17β-estradiol in this cell type but not in breast cancer cells, another estrogen-responsive tissue. Chromatin immunoprecipitation sequencing (chromatin immunoprecipitation sequencing) reveals that estrogen receptor α (ERα) binds to chromatin near GATA4 at five different enhancers. GATA4 and ERα are both recruited to ERα binding sites near genes that are specifically expressed in osteoblasts and control osteoblast differentiation. Maximal binding of GATA4 precedes ERα binding, and GATA4 is necessary for histone 3 lysine 4 dimethylation at ERα binding sites, suggesting that GATA4 is a pioneer factor for ERα. As such, knockdown of GATA4 reduced recruitment of ERα to DNA. Our study illustrates that GATA4 is a pioneer factor for ERα recruitment to osteoblast-specific enhancers.
雌激素调节成骨细胞的分化和矿化。我们确定GATA4是一种在成骨细胞中表达的转录因子，在这种细胞类型中直接受17β-雌二醇调控，而在另一种雌激素反应性组织乳腺癌细胞中则不受调控。染色质免疫沉淀测序显示，雌激素受体α（ERα）在五个不同的增强子处与GATA4附近的染色质结合。GATA4和ERα都被招募到成骨细胞中特异性表达并控制成骨细胞分化的基因附近的ERα结合位点。GATA4的最大结合先于ERα结合，并且GATA4对于ERα结合位点处组蛋白3赖氨酸4二甲基化是必需的，这表明GATA4是ERα的先驱因子。因此，敲低GATA4会减少ERα与DNA的结合。我们的研究表明，GATA4是ERα招募到成骨细胞特异性增强子的先驱因子。
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