A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30228260.
- Also identified by DOI 10.1038/s41467-018-06235-9 and PMC identifier 6143588.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Chromosomal Proteins, Non-Histone
- Gene Expression Regulation
- Mi-2 Nucleosome Remodeling and Deacetylase Complex
- RNA Polymerase II
- Transcription Elongation, Genetic