Open AccessGATA4 Regulates Estrogen Receptor-α-Mediated Osteoblast Transcription
Author(s) -
Gustavo A. Miranda-Carboni,
Miriam Güemes,
Scott Bailey,
Edgar Anaya,
Mirko Corselli,
Bruno Péault,
Susan A. Krum
Publication year - 2011
Publication title -
molecular endocrinology
Language(s) - Uncategorized
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2010-0463
Subject(s) - chromatin immunoprecipitation , biology , gata4 , osteoblast , transcription factor , estrogen receptor , estrogen receptor alpha , gene knockdown , enhancer , microbiology and biotechnology , estrogen receptor beta , chromatin , promoter , genetics , gene expression , gene , cancer , breast cancer , in vitro
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.