Functions And Molecular Mechanisms Of CARM1-NuRD Complex In Gene Transcriptional Control

The nucleosome remodeling and deacetylase(NuRD)complex is a large multisubunit complex that couples ATP-dependent chromatin-remodeling and histone deacetylase activities.In recent years,with the popularity of whole-genome highthroughput sequencing,emerging evidence suggested that NuRD is prevalently associated with gene transcriptional activation,but little is known about the underlying molecular mechanisms.Here,we reported that the transcriptional coactivator CARM1 is an integral component of NuRD,expanding the activities of NuRD to include arginine methylation,and named this complex NuRD AM(Nucleosome Remodeling,histone Deacetylation and Arginine Methylation).NuRD AM binds and activates a large cohort of genes,including those implicated in cell cycle control,to facilitate the G1/S transition.This gene activation process requires CARM1 to catalyze methylation of histone H3 and a key subunit in NuRD AM,GATAD2A/2B.The biological significance of this gene activation mechanism is underscored by the high expression of NuRD AM in breast cancers,which proves to be critical for breast cancer cell growth in vitro and tumorigenesis in vivo.These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.