Transcription Factors and Nuclear Receptors Interact with the SWI/SNF Complex through the BAF60c Subunit

Abstract

Transcriptional activity relies on coregulators that modify chromatin structure or serve as bridging factors between transcription factors and the basal transcription machinery. We identified a new coregulator of peroxisome proliferator-activated receptor γ, BRG1/nBrm-associated factor of 60 kDa, subunit c2 (BAF60c2), in a yeast two-hybrid screen of a human adipose tissue cDNA library. BAF60c2 represents a new isoform of BAF60c, a component of the SWI/SNF (mating type switching/sucrose non-fermenting) chromatin remodeling complex. This new isoform as well as the previously identified protein, renamed BAF60c1, is localized primarily in the cell nucleus and is expressed in a wide variety of tissues. Both BAF60c isoforms bind to several nuclear receptors and transcription factors of various families. BAF60c proteins interact in a ligand-independent manner with peroxisome proliferator-activated receptor γ and enhance its transcriptional activity. Both isoforms are enriched in the central nervous system and also modulate the transcriptional activity of retinoic acid-related orphan receptor α1. In conclusion, BAF60c represents a new coregulator that constitutes an important anchoring point by which the SWI/SNF complex is recruited to nuclear receptors and other transcription factors.