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

Retinoid receptors behave as ligand-dependent transcriptional regulators, r epressing transcription in the absence of ligand and activating transcripti on in its presence. The different effects on transcription are carried out through recruitment of co-regulators: unliganded receptors bind corepressor s (NCoR and SMRT) that are found within a complex containing histone deacet ylase (HDAC) activity, whereas liganded receptors recruit coactivators with histone acetylase activity (HATs). Chromatin remodeling activities have al so shown to be required, suggesting a hierarchy of promoter structure modif ications in RA target genes carried out by multiple coregulatory complexes. In this review, we examine the experimental evidence for the model just sk etched. We focus on recent findings highlighting new molecular details in r eceptor-coregulator interactions, including the discovery and initial chara cterisation of novel complexes with multiple chromatin modifying activities . Finally, we look at the role of aberrant recruitment of the NCoR-HDAC com plex by altered retinoid receptors in the pathogenesis of acute promyelocyt ic leukemia. These results point to a crucial role for control of transcrip tion factor-coregulator interactions in the regulation of cellular processe s, and suggest new molecular targets for cancer therapy.