CARM1 is an integral component of the NuRD chromatin remodeling complex

The nucleosome remodeling and deacetylase (NuRD) complex is a large multi-subunit complex that couples ATP-dependent chromatin-remodeling and histone deacetylase activities. Emerging evidence suggested that the NuRD complex 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 the NuRD complex, expanding the activities of the NuRD complex to include arginine methylation. CARM1-associated NuRD 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 3 and a key subunit of the NuRD complex, GATAD2A/2B. The biological significance of this gene activation mechanism is underscored by the coordinated expression of both CARM1 and NuRD 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. Overall design: ChIP-seq performed in this study was designed to understand the molecular mechanisms underlying CARM1/NuRD in gene transcription activation.