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Transcriptional regulation by chromatin is a highly dynamic process directed through the recruitment and coordinated action of epigenetic modifiers and readers of these modifications. Using an unbiased proteomic approach to find interactors of H3K36me3, a modification enriched on active chromatin, here we identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66α/β, and CHD3/4. PWWP2A competes with MBD3 for binding to MTA1, thus defining a new variant NuRD complex that is mutually exclusive with the MBD2/3 containing NuRD. In mESCs, PWWP2A/B is most enriched at highly transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation predominantly at highly expressed genes, accompanied by decreases in Pol II elongation. Collectively, these findings suggest a role for PWWP2A/B in regulating transcription through the fine-tuning of histone acetylation dynamics at actively transcribed genes.

Original publication

DOI

10.1038/s41467-018-06235-9

Type

Journal article

Journal

Nat Commun

Publication Date

18/09/2018

Volume

9

Keywords

Acetylation, Animals, Chromosomal Proteins, Non-Histone, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Gene Knockout Techniques, HEK293 Cells, HeLa Cells, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Mouse Embryonic Stem Cells, Nucleosomes, Proteomics, RNA Polymerase II, Transcription Elongation, Genetic