Fig. 7
From: PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex
Model of PWWP2A recruitment to chromatin and binding to M1HR complex. PWWP2A is able to interact with different chromatin states via distinct domains. It binds weakly to H3K36me3-enriched gene body regions using aromatic cage residues in its S_PWWP domain and recognizes free nucleic acid strands with the PWWP domain. Additionally, PWWP2A binds strongly to H2A.Z-containing promoter and regulatory sites with the IN domain interacting with linker DNA and the IC region mediating H2A.Z–nucleosome specificity. On chromatin, PWWP2A serves as adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes. Notably, H2A.Z-bound PWWP2A interacts with a MTA1-specific core NuRD complex (M1HR), preventing formation of full NuRD (+CHD/MBD/GATA subunits) by competing with the MTA-MBD interaction. PWWP2A thereby leads to the recruitment of HDAC1/2 to promoter and regulatory regions, resulting in turn in the deacetylation of nearby H3K27 and H2A.Z. This activity could dampen transcriptional output by reducing acetylation of regulatory regions to prevent hyperacetylation at active genomic sites
