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

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

  • Nat Commun. 2018 Sep 18;9(1):3798. doi: 10.1038/s41467-018-06235-9.
Tianyi Zhang 1,  Guifeng Wei 1,  Christopher J Millard 2,  Roman Fischer 3,  Rebecca Konietzny 3 4,  Benedikt M Kessler 3,  John W R Schwabe 2,  Neil Brockdorff 5
Affiliations

Affiliations

  • 1 Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, United Kingdom.
  • 2 Leicester Institute for Structural and Chemical Biology and Department of Molecular and Cell Biology, University of Leicester, Leicester, LE1 7RH, United Kingdom.
  • 3 Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, United Kingdom.
  • 4 Agilent Technologies, Hewlett-Packard-Str. 8, 76337, Waldbronn, Germany.
  • 5 Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, United Kingdom. neil.brockdorff@bioch.ox.ac.uk.
PMID: 30228260 DOI: 10.1038/s41467-018-06235-9
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.

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