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

ABSTRACT: Transcriptional regulation in response to thyroid hormone (3,5,3´-triiodo-L-thyronine, 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 TRb, map changes in chromatin accessibility, and capture the transcriptomic changes in response to T3 in normal human thyroid cells. There are significant shifts in TRb 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 TRb binding sites, revealing novel differential functions in regulating chromatin accessibility and gene expression. Our findings highlight three distinct modes of TRb interaction with chromatin and coordination of coregulator activity.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell Of Thyroid Gland, Thyroid Gland

DISEASE(S): Thyroid Gland Disease

SUBMITTER: Noelle Gillis  

LAB HEAD: Frances Carr

PROVIDER: PXD030403 | Pride | 2022-04-04

REPOSITORIES: Pride