Genome-Wide Mapping of In Vivo ERα-Binding Sites in Male Mouse Efferent Ductules.

As an important nuclear hormone receptor, estrogen receptor α (ERα), which is encoded by the Esr1 gene, regulates the expression of hundreds of genes in a stimulus-specific, temporal, and tissue-specific fashion, mainly by binding to specific DNA sequences called estrogen response elements (EREs). As an important estrogen target tissue in males, the function of the efferent ductules relies on the presence of the ERα protein, but the underlying regulatory mechanisms are poorly illustrated. In this study, genome-wide ERα-binding sites in mouse efferent ductules were mapped by chromatin immunoprecipitation sequencing. In total, 12,105 peaks were identified, and a majority of them were located far from the annotated gene transcription start site. Motif analysis revealed that ∼80% of the ERα-binding peaks harbored at least one ERE, whereas androgen response element-like sequences were the most overrepresented motif in the peaks without any EREs. A number of candidate transcription factor motifs adjacent to the EREs were significantly enriched, including AP2 and GRE, implying the involvement of these putative adjacent factors in the global regulation of ERα target genes. Unexpectedly, more than 50% of the ERα-binding peaks in mouse efferent ductules overlapped with those binding peaks previously identified in mouse uterus, suggesting the conserved mechanism of ERα action in these two tissues. Cobinding of ERα target genes by androgen receptor was further confirmed for Slc9a3 gene, which was responsible for fluid resorption in the efferent ductules. Taken together, our study provides a useful reference set for future work aimed at exploring the mechanism of ERα action in physiological conditions.