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

Semin Cell Dev Biol. 1999 Apr;10(2):215-25. doi: 10.1006/scdb.1999.0303.

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 corepressors (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 NCoRHDAC 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.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism
  • Animals
  • Binding Sites
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin / ultrastructure
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Gene Expression Regulation, Leukemic
  • Histone Acetyltransferases
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Leukemia, Promyelocytic, Acute / metabolism
  • Ligands
  • Macromolecular Substances
  • Models, Genetic
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • Nucleosomes / genetics
  • Nucleosomes / ultrastructure
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Protein Processing, Post-Translational
  • Receptors, Retinoic Acid / chemistry
  • Receptors, Retinoic Acid / drug effects
  • Receptors, Retinoic Acid / physiology*
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / metabolism
  • Retinoids / pharmacology
  • Saccharomyces cerevisiae Proteins*
  • Trans-Activators / metabolism
  • Transcription, Genetic / physiology
  • Translocation, Genetic

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • Ligands
  • Macromolecular Substances
  • NCOR1 protein, human
  • NCOR2 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Co-Repressor 2
  • Nucleosomes
  • Oncogene Proteins, Fusion
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Retinoids
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • DNA
  • Acetyltransferases
  • Histone Acetyltransferases
  • Histone Deacetylases