NuRD-interacting protein ZFP296 regulates genome-wide NuRD localization and differentiation of mouse embryonic stem cells (ChIP-seq)

The Nucleosome Remodeling and Deacetylase (NuRD) complex plays an important role in gene expression regulation, stem cell self-renewal, and lineage commitment. Yet little is known about the dynamics of NuRD during cellular differentiation. Here, we study these dynamics using genome-wide profiling and quantitative interaction proteomics in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). The genomic targets of NuRD are highly dynamic during differentiation, with most binding occurring at cell-type specific promoters and enhancers. We identify ZFP296 as a novel, ESC-specific NuRD interactor that also interacts with the SIN3A complex. ChIP-sequencing in Zfp296 knockout (KO) ESCs reveals decreased NuRD binding both genome-wide and at ZFP296 binding sites, although this has little effect on the transcriptome. Nevertheless, Zfp296 KO ESCs exhibit delayed induction of lineage-specific markers upon differentiation to embryoid bodies. In summary, we identify an ESC-specific NuRD interacting protein which regulates genome-wide NuRD binding and cellular differentiation. ChIP-seq samples for H3K4me1, H3K4me3, H3K27ac, H3K27me3, MBD3, CHD4, and corresponding inputs from wildtype ESCs and NPCs. ChIP-seq for GFP-ZFP296 and SIN3A in wildtype ESCs. ChIP-seq with spike-in for MBD3, CHD4, SIN3A, H3K27ac, and corresponding inputs in wildtype and Zfp296 KO ESCs.