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PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex

Author

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  • Stephanie Link

    (BioMedical Center (BMC), Ludwig-Maximilians-University Munich
    Institute for Genetics, Justus-Liebig University Giessen)

  • Ramona M. M. Spitzer

    (BioMedical Center (BMC), Ludwig-Maximilians-University Munich
    Institute for Genetics, Justus-Liebig University Giessen)

  • Maryam Sana

    (School of Life and Environmental Sciences, University of Sydney)

  • Mario Torrado

    (School of Life and Environmental Sciences, University of Sydney)

  • Moritz C. Völker-Albert

    (BioMedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Eva C. Keilhauer

    (Max Planck Institute of Biochemistry
    Coriolis Pharma)

  • Thomas Burgold

    (University of Cambridge
    Wellcome Sanger Institute, Wellcome Genome Campus)

  • Sebastian Pünzeler

    (BioMedical Center (BMC), Ludwig-Maximilians-University Munich
    Coparion GmbH & Co. KG)

  • Jason K. K. Low

    (School of Life and Environmental Sciences, University of Sydney)

  • Ida Lindström

    (School of Life and Environmental Sciences, University of Sydney)

  • Andrea Nist

    (Genomics Core Facility, Philipps-University Marburg)

  • Catherine Regnard

    (BioMedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Thorsten Stiewe

    (Genomics Core Facility, Philipps-University Marburg
    Institute for Molecular Oncology, Philipps-University Marburg)

  • Brian Hendrich

    (University of Cambridge)

  • Axel Imhof

    (BioMedical Center (BMC), Ludwig-Maximilians-University Munich
    Center for Integrated Protein Science Munich (CIPSM))

  • Matthias Mann

    (Max Planck Institute of Biochemistry
    Center for Integrated Protein Science Munich (CIPSM))

  • Joel P. Mackay

    (School of Life and Environmental Sciences, University of Sydney)

  • Marek Bartkuhn

    (Institute for Genetics, Justus-Liebig University Giessen)

  • Sandra B. Hake

    (Institute for Genetics, Justus-Liebig University Giessen
    Center for Integrated Protein Science Munich (CIPSM))

Abstract

Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial–facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.

Suggested Citation

  • Stephanie Link & Ramona M. M. Spitzer & Maryam Sana & Mario Torrado & Moritz C. Völker-Albert & Eva C. Keilhauer & Thomas Burgold & Sebastian Pünzeler & Jason K. K. Low & Ida Lindström & Andrea Nist &, 2018. "PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06665-5
    DOI: 10.1038/s41467-018-06665-5
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    Cited by:

    1. 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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