GSE21777
Unbiased, Genome-wide in vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-specific Liver Gene Expression
We have used a simple and efficient method to identify condition-specific transcriptional regulatory sites in vivo to help elucidate the molecular basis of sex-differences in transcription, which are widespread in mammalian tissues and affect normal physiology, drug response, inflammation and disease.  To systematically uncover transcriptional regulators responsible for these differences, we used DNase hypersensitivity analysis coupled with high-throughput sequencing to produce condition-specific maps of regulatory sites in male and female mouse liver, and for livers of male mice feminized by continuous infusion of growth hormone (GH).  We identified 71,264 hypersensitive sites, with 1,284 showing robust sex-differences.  Continuous GH infusion suppressed the vast majority of male-specific sites and induced a subset of female-specific sites in male liver.  We also identified broad genomic regions (up to ~100kb) showing sex-dependent hypersensitivity and similar patterns of GH response. We found a strong association of sex-specific sites with sex-specific transcription; however, a majority of sex-specific sites were >100kb from sex-specific genes.  By analyzing sequence motifs within regulatory regions, we identified two known regulators of liver sexual dimorphism, and several new candidates for further investigation.  This approach can readily be applied to mapping condition-specific regulatory sites in mammalian tissues under a wide variety of physiological conditions. Overall design: Global DNase Hypersensitivity in male, female, and continuous growth hormone-treated male mouse liver tissue. 10 samples: Male liver (2 replicates), Female liver (2 replicates), GH-treated male liver (2 replicates), DNase digested genomic control (from male and female liver separately) and sonicated genomic control (from male and female liver separately).