西亚试剂：Research Resource: Genome-Wide Mapping of in Vivo Androgen

Research Resource: Genome-Wide Mapping of in Vivo Androgen Receptor Binding Sites in Mouse Epididymis
Shuanggang Hu, Guangxin Yao, Xiaojun Guan, Zimei Ni, Wubin Ma, Elizabeth M. Wilson, Frank S. French, Qiang Liu*, and Yonglian Zhang*

Shanghai Key Laboratory for Molecular Andrology (S.H., G.Y., Z.N., W.M., Q.L., Y.Z.), State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School (S.H., W.M.), Chinese Academy of Sciences, Shanghai 20031, China; Shanghai Institute of Planned Parenthood Research (Y.Z.), Shanghai 200032, China; Center for Bioinformatics (X.G.) and Laboratories for Reproductive Biology (E.M.W., F.S.F.), Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and School of Life Science and Biopharmaceutics (G.Y.), Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, China

Epididymal function depends on androgen signaling through the androgen receptor (AR), although most of the direct AR target genes in epididymis remain unknown. Here we 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.

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