Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription.
A contemporary view of hormone action at the transcriptional level requires knowledge of the transcription factors including the hormone receptor that may bind to promoters or enhancers, together with the chromosomal context within which these regulatory proteins function. Nuclear receptors provide the best examples of transcriptional control through the targeted recruitment of large protein complexes that modify chromosomal components and reversibly stabilize or destabilize chromatin. Ligand-dependent recruitment of transcriptional coactivators destabilizes chromatin by mechanisms including histone acetylation and contacts with the basal transcriptional machinery. In contrast, the recruitment of corepressors in the absence of ligand or in the presence of hormone antagonists serves to stabilize chromatin by the targeting of histone deacetylases. Both activation and repression require the action of other chromatin remodeling engines of the switch 2/sucrose non-fermentable 2 (SWI2/SNF2) class. Here we summarize this information and integrate hormone action into a chromatin context.
Collingwood
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Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, Maryland 20892-5431, USA.
Urnov
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Wolffe
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AP
D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
D002843:Chromatin; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases