Thyroid hormone dependent transcriptional programming by TR beta requires SWI/SNF chromatin remodelers

Transcriptional regulation in response to thyroid hormone (3,5,3 '-triiodo-l-thyronine, T-3) is a dynamic and cell-type specific process that maintains cellular homeostasis and identity in all tissues. However, our understanding of the mechanisms of thyroid hormone receptor (TR) actions at the molecular level are actively being refined. We used an integrated genomics approach to profile and characterize the cistrome of TR beta, map changes in chromatin accessibility, and capture the transcriptomic changes in response to T-3 in normal human thyroid cells. There are significant shifts in TR beta genomic occupancy in response to T-3, which are associated with differential chromatin accessibility, and differential recruitment of SWI/SNF chromatin remodelers. We further demonstrate selective recruitment of BAF and PBAF SWI/SNF complexes to TR beta binding sites, revealing novel differential functions in regulating chromatin accessibility and gene expression. Our findings highlight three distinct modes of TR beta interaction with chromatin and coordination of coregulator activity.