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PMID: 9430643 Published · ppublish English Journal Article

Distinct requirements for chromatin assembly in transcriptional repression by thyroid hormone receptor and histone deacetylase.

The EMBO journal ·Vol. 17 ·No. 2 ·1998-01-15 ·Pages 520-34

Wong J, Patterton D, Imhof A, Guschin D, Shi YB, Wolffe AP

Abstract

Histone deacetylase and chromatin assembly contribute to the control of transcription of the Xenopus TRbetaA gene promoter by the heterodimer of Xenopus thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR). Addition of the histone deacetylase inhibitor Trichostatin A (TSA) relieves repression of transcription due to chromatin assembly following microinjection of templates into Xenopus oocyte nuclei, and eliminates regulation of transcription by TR-RXR. Expression of Xenopus RPD3p, the catalytic subunit of histone deacetylase, represses the TRbetaA promoter, but only after efficient assembly of the template into nucleosomes. In contrast, the unliganded TR-RXR represses templates only partially assembled into nucleosomes; addition of TSA also relieves this transcriptional repression. This result indicates the distinct requirements for chromatin assembly in mediating transcriptional repression by the deacetylase alone, compared with those needed in the presence of unliganded TR-RXR. In addition, whereas hormone-bound TR-RXR targets chromatin disruption as assayed through changes in minichromosome topology and loss of a regular nucleosomal ladder on micrococcal nuclease digestion, addition of TSA relieves transcriptional repression but does not disrupt chromatin. Thus, TR-RXR can facilitate transcriptional repression in the absence of hormone through mechanisms in addition to recruitment of deacetylase, and disrupts chromatin structure through mechanisms in addition to the inhibition or release of deacetylase.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Catalysis Chromatin/genetics,metabolism,physiology DNA Replication/genetics Gene Expression Regulation/drug effects Histone Deacetylase Inhibitors Histone Deacetylases/biosynthesis,genetics,physiology Hydroxamic Acids/pharmacology Ligands Molecular Sequence Data Nucleosomes/genetics,metabolism Receptors, Retinoic Acid/physiology Receptors, Thyroid Hormone/physiology Retinoid X Receptors Templates, Genetic Thyroid Hormones/pharmacology Transcription Factors/antagonists & inhibitors,biosynthesis,genetics,physiology Transcription, Genetic/drug effects Xenopus
Chemicals
Chromatin Histone Deacetylase Inhibitors Hydroxamic Acids Ligands Nucleosomes Receptors, Retinoic Acid Receptors, Thyroid Hormone Retinoid X Receptors Thyroid Hormones Transcription Factors trichostatin A Histone Deacetylases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wong J
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, MD 20892-5431, USA.
Patterton D
Imhof A
Guschin D
Shi Y B
Wolffe A P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1998-01-15
Pages
520-34
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170402
Subset
IM
Databases
GENBANK
AF020658
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