chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity染色质易访问性揭示了洞察雄激素受体激活转录特异性.pdfVIP

Tewari et al. Genome Biology 2012, 13:R88 /2012/13/10/R88 RESEARCH Open Access Chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity 1 1 1 1 1 3 Alok K Tewari , Galip Gürkan Yardimci , Yoichiro Shibata , Nathan C Sheffield , Lingyun Song , Barry S Taylor , 1 4,5 1,6,7 8 1,9† Stoyan G Georgiev , Gerhard A Coetzee , Uwe Ohler , Terrence S Furey , Gregory E Crawford and Phillip G Febbo2,10,11*† Abstract Background: Epigenetic mechanisms such as chromatin accessibility impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of the male phenotype and prostate cancer pathogenesis, acts primarily through ligand-activated transcription of target genes. Although several determinants of AR transcriptional specificity have been elucidated, our understanding of the interplay between chromatin accessibility and AR function remains incomplete. Results: We used deep sequencing to assess chromatin structure via DNase I hypersensitivity and mRNA abundance, and paired these datasets with three independent AR ChIP-seq datasets. Our analysis revealed qualitative and quantitative differences in chromatin accessibility that corresponded to both AR binding and an enrichment of motifs for potential collaborating factors, one of which was identified as SP1. These quantitative differences were significantly associated with AR-regulated mRNA transcription across the genome. Base-pair resolution of the DNase I cleavage profile revealed three distinct footprinting