A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes

Tianyi Zhang, Guifeng Wei, Christopher J. Millard, Roman Fischer, Rebecca Konietzny, Benedikt M. Kessler, John W. R. Schwabe and Neil Brockdorff ()
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Tianyi Zhang: University of Oxford
Guifeng Wei: University of Oxford
Christopher J. Millard: University of Leicester
Roman Fischer: University of Oxford, Roosevelt Drive
Rebecca Konietzny: University of Oxford, Roosevelt Drive
Benedikt M. Kessler: University of Oxford, Roosevelt Drive
John W. R. Schwabe: University of Leicester
Neil Brockdorff: University of Oxford

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06235-9

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