Retinoid receptors in health and disease: Co-regulators and the chromatin connection

Research output: Contribution to journalArticle

Abstract

Retinoid receptors behave as ligand-dependent transcriptional regulators, repressing transcription in the absence of ligand and activating transcription in its presence. The different effects on transcription are carried out through recruitment of co-regulators: unliganded receptors bind compressors (NCoR and SMRT) that are found within a complex containing histone deacetylase (HDAC) activity, whereas liganded receptors recruit coactivators with histone acetylase activity (HATs). Chromatin remodeling activities have also shown to be required, suggesting a hierarchy of promoter structure modifications in RA target genes carried out by multiple coregulatory complexes. In this review, we examine the experimental evidence for the model just sketched. We focus on recent findings highlighting new molecular details in receptor-coregulator interactions, including the discovery and initial characterisation of novel complexes with multiple chromatin modifying activities. Finally, we look at the role of aberrant recruitment of the NCoR-HDAC complex by altered retinoid receptors in the pathogenesis of acute promyelocytic leukemia. These results point to a crucial role for control of transcription factor-coregulator interactions in the regulation of cellular processes, and suggest new molecular targets for cancer therapy.

Original languageEnglish
Pages (from-to)215-225
Number of pages11
JournalSeminars in Cell and Developmental Biology
Volume10
Issue number2
Publication statusPublished - Apr 1999

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Histone Deacetylases
Retinoids
Chromatin
Ligands
Histone Acetyltransferases
Acute Promyelocytic Leukemia
Chromatin Assembly and Disassembly
Health
Transcription Factors
Theoretical Models
Genes
Neoplasms
Therapeutics

Keywords

  • Histone acetylation
  • Nuclear co-activators
  • Nuclear co-repressors
  • Retinoids
  • RXR-RAR heterodimers

ASJC Scopus subject areas

  • Developmental Biology

Cite this

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abstract = "Retinoid receptors behave as ligand-dependent transcriptional regulators, repressing transcription in the absence of ligand and activating transcription in its presence. The different effects on transcription are carried out through recruitment of co-regulators: unliganded receptors bind compressors (NCoR and SMRT) that are found within a complex containing histone deacetylase (HDAC) activity, whereas liganded receptors recruit coactivators with histone acetylase activity (HATs). Chromatin remodeling activities have also shown to be required, suggesting a hierarchy of promoter structure modifications in RA target genes carried out by multiple coregulatory complexes. In this review, we examine the experimental evidence for the model just sketched. We focus on recent findings highlighting new molecular details in receptor-coregulator interactions, including the discovery and initial characterisation of novel complexes with multiple chromatin modifying activities. Finally, we look at the role of aberrant recruitment of the NCoR-HDAC complex by altered retinoid receptors in the pathogenesis of acute promyelocytic leukemia. These results point to a crucial role for control of transcription factor-coregulator interactions in the regulation of cellular processes, and suggest new molecular targets for cancer therapy.",
keywords = "Histone acetylation, Nuclear co-activators, Nuclear co-repressors, Retinoids, RXR-RAR heterodimers",
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