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 nonfermentable 2 (SWI2/SNF2) class. Here we summarize this information and integrate hormone action into a chromatin context. Journal of Molecular Endocrinology (1999) 23, 255-275 INTRODUCTIONThe nuclear hormone receptors provide transcription research with a clear example of how the reversible modification of chromatin structure can contribute to the control of gene expression. Remarkable progress in the definition of intermediary protein complexes that activate or repress transcription has allowed common themes in transcriptional control by a wide variety of receptors to emerge. The roles of these coactivators and corepressors in mediating the activities of nuclear receptors within chromatin is a key element of contemporary molecular endocrinology. The beststudied receptors in this regard are those for the glucocorticoid and thyroid hormones.The glucocorticoid receptor recognizes response elements within nucleosomes as a first step towards a finely orchestrated rearrangement of histone-DNA contacts concomitant with the assembly of a functional transcription complex. The determinants of chromatin remodeling and the molecular machines that carry it out are now understood in considerable detail. Likewise, the thyroid hormone receptor recognizes nucleosomal DNA and utilizes chromatin to regulate transcription. However, in this case the receptor exerts a dual function. In the absence of ligand, the thyroid hormone receptor recruits a corepressor complex that stabilizes chromatin structure. Upon addition of hormone the receptor releases this repressive complex, and recruits coactivators that destabilize chromatin and promote transcription.This review illustrates the role of chromatin, coactivators and corepressors in gene control as orchestrated by the glucocorticoid and thyroid hormone receptors. COACTIVATORS AND COREPRESSORS CoactivatorsThe interplay of distinct nuclear receptor responsive transcription pathways has been recognized for 255
The genome of Xenopus laevis contains two large families of class III genes (oocyte 5S RNA and satellite I DNA) that are repressed in somatic cells. Both gene families are actively transcribed in a soluble extract of X.laevis oocyte nuclei, using chromatin deficient in histone H1 as a template. The addition of histone H1, to this transcriptionally active chromatin, results in the dominant and selective repression of oocyte 5S RNA genes and satellite I DNA. Somatic 5S RNA genes remain active following histone H1 addition. Changes in chromatin structure could have a dominant role in the regulation of class III gene expression during Xenopus embryogenesis.
No abstract
An extract of whole oocytes (oocyte S150) differentially transcribes Xenopus oocyte and somatic 5S RNA genes. In the oocyte S150, transcription complexes with different stabilities are assembled onto oocyte and somatic 5S DNA. The stability of the transcription complex is dependent on activities present in a fraction containing transcription factor TFIIIC. This fraction stabilizes the binding of the positive transcription factor TFIIIA to a somatic 5S RNA gene much more efficiently than it does to an oocyte gene. The oocyte S150 transcription extract is deficient in TFIIIC such that supplementation with a fraction enriched in this transcription factor selectively stimulates oocyte 5S DNA transcription. Previously it has been shown that an egg extract deficient in TFIIIA selectively transcribes somatic 5S RNA genes. Thus under conditions where there is differential stability of transcription complexes, limitation of either TFIIIA or TFIIIC may exaggerate the differential expression of two genes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.