Retinoid-dependent recruitment of a histone H1 displacement activity by retinoic acid receptor

Targeted recruitment of histone acetyltransferase (HAT) activities by seque nce-specific transcription factors, including the retinoic acid receptors ( RARs) and retinoid X receptors (RXRs), has been proposed to lead to destabi lization of nucleosomal cores by acetylation of core histones, However, bio chemical evidence indicates that destabilization and depletion of linker H1 histones must also occur at the promoter regions of actively transcribing genes. Mechanisms by which nuclear receptors and other transcription factor s affect the removal of histone H1 from transcriptionally silent chromatin have not been previously described, In this report, we show that RARs inter act in a ligand-dependent manner with HMG-I, which is known to displace his tone H1 from chromatin, We further show that HMG-I and a novel related prot ein, HMG-R, also interact with other transcription factors. Using sense and antisense constructs of HMG-I/R in transient transfection assays with a re tinoid responsive reporter, we also demonstrate that HMG-IIR is important f or retinoid dependent transcriptional activity of RAR. These findings sugge st a step wise mechanism by which RARs and other transcription factors can cause a targeted unfolding of compact chromatin as a first step in transcri ptional activation, which would then be followed by recruitment of HAT acti vity and subsequent events.