HRP2-DPF3a-BAF complex coordinates histone modification and chromatin remodeling to regulate myogenic gene transcription [ChIP-Seq]

Functional crosstalk between histone modifications and chromatin remodeling has emerged as a key regulatory mode of transcriptional control during cell fate decisions, but the underlying mechanisms are not fully understood. Here we demonstrate that HRP2-DPF3a-BAF complex coordinates histone H3 lysine 36 methylation (H3K36me) and ATP-dependent chromatin remodeling to regulate chromatin dynamic and gene transcription during myogenic differentiation. Mechanistically, through its HIV integrase binding domain (IBD), HRP2 associates with BRG1/BRM associated factor (BAF) chromatin remodeling complex by direct interaction with BAF45c (DPF3a) subunit. Through its Pro-Trp-Trp-Pro (PWWP) domain, HRP2 preferentially binds to H3K36me2. Consistent with the biochemical studies, genome-wide analyses show that HRP2 colocalizes with DPF3a at gene promoters enriched for H3K36me2. Overall design: Examination of binding of Hrp2 in mouse myoblasts and myotubes by ChIP-seq. Examination of binding of Dpf3a and H3K36me2 in mouse myotubes by ChIP-seq.