title: GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription.
abstract: 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.
authors.affiliation: 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.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Miranda-Carboni
authors.forename: Miriam
authors.initials: M
authors.lastname: Guemes
authors.forename: Shannon
authors.initials: S
authors.lastname: Bailey
authors.forename: Edgar
authors.initials: E
authors.lastname: Anaya
authors.forename: Mirko
authors.initials: M
authors.lastname: Corselli
authors.forename: Bruno
authors.initials: B
authors.lastname: Peault
authors.forename: Susan A
authors.initials: SA
authors.lastname: Krum
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology; D053222:Fas Ligand Protein / Q000235:genetics; D005269:Femur / Q000166:cytology / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D011485:Protein Binding; D012886:Skull / Q000166:cytology / Q000378:metabolism; D046509:Tissue Culture Techniques; D014158:Transcription, Genetic
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047628:Estrogen Receptor alpha; D004967:Estrogens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; C493716:Runx2 protein, mouse; D000469:Alkaline Phosphatase