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

Author

Listed:
  • 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
    Agilent Technologies, Hewlett-Packard-Str. 8)

  • Benedikt M. Kessler

    (University of Oxford, Roosevelt Drive)

  • John W. R. Schwabe

    (University of Leicester)

  • Neil Brockdorff

    (University of Oxford)

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.

Suggested Citation

  • Tianyi Zhang & Guifeng Wei & Christopher J. Millard & Roman Fischer & Rebecca Konietzny & Benedikt M. Kessler & John W. R. Schwabe & Neil Brockdorff, 2018. "A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06235-9
    DOI: 10.1038/s41467-018-06235-9
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    Cited by:

    1. Nina Schmolka & Ino D. Karemaker & Richard Cardoso da Silva & Davide C. Recchia & Vincent Spegg & Jahnavi Bhaskaran & Michael Teske & Nathalie P. Wagenaar & Matthias Altmeyer & Tuncay Baubec, 2023. "Dissecting the roles of MBD2 isoforms and domains in regulating NuRD complex function during cellular differentiation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Carlos Rivera & Hun-Goo Lee & Anna Lappala & Danni Wang & Verónica Noches & Montserrat Olivares-Costa & Marcela Sjöberg-Herrera & Jeannie T. Lee & María Estela Andrés, 2022. "Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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