Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling

Lars Grøntved, Joshua J Waterfall, Dong Wook Kim, Songjoon Baek, Myong-Hee Sung, Li Zhao, Jeong Won Park, Ronni Nielsen, Robert L Walker, Yuelin J Zhu, Paul S Meltzer, Gordon L Hager, Sheue-Yann Cheng

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number7048
JournalNature Communications
Volume6
ISSN2041-1723
DOIs
Publication statusPublished - 2015

Fingerprint

Thyroid Hormone Receptors
chromatin
Chromatin Assembly and Disassembly
hormones
Transcriptional Activation
Chromatin
Chemical activation
activation
Ligands
ligands
Transcription
Hormones
Co-Repressor Proteins
Genes
Steroid hormones
Deoxyribonucleases
Liver
Switches
steroids
Tissue

Cite this

Grøntved, Lars ; Waterfall, Joshua J ; Kim, Dong Wook ; Baek, Songjoon ; Sung, Myong-Hee ; Zhao, Li ; Park, Jeong Won ; Nielsen, Ronni ; Walker, Robert L ; Zhu, Yuelin J ; Meltzer, Paul S ; Hager, Gordon L ; Cheng, Sheue-Yann. / Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling. In: Nature Communications. 2015 ; Vol. 6.
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title = "Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling",
abstract = "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.",
author = "Lars Gr{\o}ntved and Waterfall, {Joshua J} and Kim, {Dong Wook} and Songjoon Baek and Myong-Hee Sung and Li Zhao and Park, {Jeong Won} and Ronni Nielsen and Walker, {Robert L} and Zhu, {Yuelin J} and Meltzer, {Paul S} and Hager, {Gordon L} and Sheue-Yann Cheng",
year = "2015",
doi = "10.1038/ncomms8048",
language = "English",
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journal = "Nature Communications",
issn = "2041-1723",
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Grøntved, L, Waterfall, JJ, Kim, DW, Baek, S, Sung, M-H, Zhao, L, Park, JW, Nielsen, R, Walker, RL, Zhu, YJ, Meltzer, PS, Hager, GL & Cheng, S-Y 2015, 'Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling', Nature Communications, vol. 6, 7048. https://doi.org/10.1038/ncomms8048

Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling. / Grøntved, Lars; Waterfall, Joshua J; Kim, Dong Wook; Baek, Songjoon; Sung, Myong-Hee; Zhao, Li; Park, Jeong Won; Nielsen, Ronni; Walker, Robert L; Zhu, Yuelin J; Meltzer, Paul S; Hager, Gordon L; Cheng, Sheue-Yann.

In: Nature Communications, Vol. 6, 7048, 2015.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling

AU - Grøntved, Lars

AU - Waterfall, Joshua J

AU - Kim, Dong Wook

AU - Baek, Songjoon

AU - Sung, Myong-Hee

AU - Zhao, Li

AU - Park, Jeong Won

AU - Nielsen, Ronni

AU - Walker, Robert L

AU - Zhu, Yuelin J

AU - Meltzer, Paul S

AU - Hager, Gordon L

AU - Cheng, Sheue-Yann

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

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