Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling.
A bimodal switch model is widely used to describe transcriptional regulation by the thyroid hormone receptor (TR). In this model, the unliganded TR forms stable, chromatin-bound complexes with transcriptional co-repressors to repress transcription. Binding of hormone dissociates co-repressors and facilitates recruitment of co-activators to activate transcription. Here we show that in addition to hormone-independent TR occupancy, ChIP-seq against endogenous TR in mouse liver tissue demonstrates considerable hormone-induced TR recruitment to chromatin associated with chromatin remodelling and activated gene transcription. Genome-wide footprinting analysis using DNase-seq provides little evidence for TR footprints both in the absence and presence of hormone, suggesting that unliganded TR engagement with repressive complexes on chromatin is, similar to activating receptor complexes, a highly dynamic process. This dynamic and ligand-dependent interaction with chromatin is likely shared by all steroid hormone receptors regardless of their capacity to repress transcription in the absence of ligand.
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.|Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
Lars
L
Grøntved
Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland 20892, USA.
Joshua J
JJ
Waterfall
Laboratory of Molecular Biology, CCR, NCI, NIH, Building 37/NIH, Bethesda, Maryland 20892, USA.
Dong Wook
DW
Kim
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Songjoon
S
Baek
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Myong-Hee
MH
Sung
Laboratory of Molecular Biology, CCR, NCI, NIH, Building 37/NIH, Bethesda, Maryland 20892, USA.
Li
L
Zhao
Laboratory of Molecular Biology, CCR, NCI, NIH, Building 37/NIH, Bethesda, Maryland 20892, USA.
Jeong Won
JW
Park
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
Ronni
R
Nielsen
Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland 20892, USA.
Robert L
RL
Walker
Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland 20892, USA.
Yuelin J
YJ
Zhu
Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland 20892, USA.
Paul S
PS
Meltzer
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Gordon L
GL
Hager
Laboratory of Molecular Biology, CCR, NCI, NIH, Building 37/NIH, Bethesda, Maryland 20892, USA.
Sheue-Yann
SY
Cheng
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000378:metabolism
D008024:Ligands; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine