SRA

Hormone dependent activation of enhancers includes histone hyperacetylation and mediator recruitment. Histone hyperacetylation is often explained by a bimodal switch mod-el, where histone deacetylases (HDACs) disassociates from chromatin and histone acetyl transferases (HATs) are recruited. This model builds on decades of research on steroid re-ceptor regulation of transcription. We have used a genomics approach to study enhancer hyperacetylation by the thyroid hormone receptor (TR) and present a revised model. 1) at poised constitutively TR bound enhancers, HATs occupy chromatin irrespective of thyroid hormone (T3) levels, whereas HDAC occupancy is regulated by T3, suggesting that HDACs functions as a histone acetylation rheostat. 2) at enhancers established in a T3 dependent manner, TR is recruited to chromatin together with HATs. 3) a number of enhancers are hy-peracetylated secondary to TR activation. Collectively, this demonstrates various mechanisms controlling hormone dependent transcription and adds significant details to the otherwise simple bimodal switch model. Overall design: ChIP-seq was performed in replicates from a pool of four individual ChIPs from livers of four individual mice. Some ChIP-seq's were not performed in replicates. The RNA-seq was performed on four indepedent biological replicates.