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

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. Ovariectomized (OVX) mice were treated with ICI, Tam or vehicle for 1h. Uterus was collected from the six mice in each treatment then put together for a sample.Each dataset was obtained from a single pool of uterine tissue (n = 6 mice)