Genome-Wide Mapping of in Vivo Androgen Receptor Binding Sites in Mouse Epididymis

The research team led by Prof. Yonglian Zhang (SIBCB) recently identified the genomic binding site of androgen receptor (AR) in Mouse Epididymis. This finding was published in Molecular Endocrinology on October 13th.

 

Epididymal function depends on androgen signaling through the AR, although most of the direct AR target genes in epididymis remain unknown. In this study, the researchers globally mapped the AR binding regions in mouse caput epididymis in which AR is highly expressed. Chromatin immunoprecipitation sequencing indicated that AR bound selectively to 19,377 DNA regions, the majority of which were intergenic and intronic. Motif analysis showed that 94% of the AR binding regions harbored consensus androgen response elements enriched with multiple binding motifs that included nuclear factor 1 and activator protein 2 sites consistent with combinatorial regulation. Unexpectedly, AR binding regions showed limited conservation across species, regardless of whether the metric for conservation was based on local sequence similarity or the presence of consensus androgen response elements. Further analysis suggested the AR target genes are involved in diverse biological themes that include lipid metabolism and sperm maturation. Potential novel mechanisms of AR regulation were revealed at individual genes such as cysteine-rich secretory protein 1. The composite studies provide new insights into AR regulation under physiological conditions and a global resource of AR binding sites in a normal androgen-responsive tissue.

 

This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Chinese Academy of Sciences, and the National Institutes of Health, USA.