Thyroid Hormone Dependent Transcriptional Programming by TRβ Requires SWI/SNF Chromatin Remodelers

Abstract

Transcriptional regulation in response to thyroid hormone (T3) 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 T3 in normal thyroid cells. There are significant shifts in TR{beta} genomic occupancy in response to T3, 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.