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August 08, 2022 preprint Open access Aachen paper

Comprehensive chromatin proteomics resolves functional phases of pluripotency

bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/2022.08.08.503208 Full text (OA) OpenAlex

Abstract

Abstract The establishment of cellular identity is driven by transcriptional and epigenetic regulation exerted by the components of the chromatin proteome - the chromatome. However, chromatome composition and its dynamics in functional phases of pluripotency have not been comprehensively analyzed thus limiting our understanding of these processes. To address this problem, we developed an accurate mass spectrometry (MS)-based proteomic method called Chromatin Aggregation Capture (ChAC) followed by Data-Independent Acquisition (DIA) to analyze chromatome reorganizations during the transition from ground to formative and primed pluripotency states. This allowed us to generate a comprehensive atlas of proteomes, chromatomes, and chromatin affinities for the three pluripotency phases, revealing the specific binding and rearrangement of regulatory complexes. The technical advances, the comprehensive chromatome atlas, and the extensive analysis reported here provide a foundation for an in-depth understanding of mechanisms that govern the phased progression of pluripotency and changes of cellular identities in development and disease.

Authors 7

  1. Enes Ugur

    Max Planck Institute of Biochemistry · Ludwig-Maximilians-Universität München

    Affiliation as printed

    Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, 82152, Germany

    Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, 81377, Germany

    Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, 815, Germany

    Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, 8377, Germany

  2. Alexandra de la Porte

    Helmholtz Munich

    Affiliation as printed

    Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany

  3. Sebastian Bultmann

    Ludwig-Maximilians-Universität München

    Affiliation as printed

    Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, 81377, Germany

    Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, 8377, Germany

  4. Micha Drukker Aachen Division of Drug Discovery and Safety Leiden Academic Centre for Drug Research

    Leiden University · Helmholtz Munich

    Affiliation as printed

    Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Gorlaeus Building, 2333 CC RA Leiden, The Netherlands

    Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany

  5. Matthias Mann corresponding

    University of Copenhagen · Novo Nordisk Foundation · Max Planck Institute of Biochemistry

    Affiliation as printed

    Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, 82152, Germany

    Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

    Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, 815, Germany

  6. Michael Wierer corresponding

    University of Copenhagen · Max Planck Institute of Biochemistry

    Affiliation as printed

    Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, 82152, Germany

    Proteomics Research Infrastructure, University of Copenhagen, DK-2200 Copenhagen, Denmark

    Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, 815, Germany

  7. Heinrich Leonhardt corresponding

    Ludwig-Maximilians-Universität München

    Affiliation as printed

    Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, 81377, Germany

    Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, 8377, Germany

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References 92