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Genome-wide mapping of ligand-dependent ERα binding sites in the ERα AF-2 mutant mouse uterus

ABSTRACT: Estrogen receptor alpha (ERα) is a ligand dependent transcription regulator, which contains two transactivation functional domains, AF-1 and AF-2. These activities are regulated differently by the ligands. Specifically, the selective estrogen receptor modulators (SERMs) regulate AF-1 rather than AF-2. It is important to know whether AF-1/AF-2 predominantly regulated genes exist in the tissues for a better understanding of the SERMs functionality. We sought out AF-1 dependent estrogenic genes by using the AF-2 mutated knock-in (KI) mouse model, AF2ERKI. AF2ER is an estrogen-insensitive AF-2 disrupted ERα mutant mouse but unique to this model, AF-1 can be activated by the estrogen-antagonists, such as fulvestrant (ICI) and 4-hydroxytamoxifen (Tam) in vitro and in vivo. The information of genome-wide ICI or Tam dependent AF-2 mutated ERα binding sites could explain the mechanism of the selective estrogenic action of SERMs through AF-1 dependent gene regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE137196 | GEO | 2019/12/10

REPOSITORIES: GEO

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