The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs
Andreas Herchenröther,
Stefanie Gossen,
Tobias Friedrich,
Alexander Reim,
Nadine Daus,
Felix Diegmüller,
Jörg Leers,
Hakimeh Moghaddas Sani,
Sarah Gerstner,
Leah Schwarz,
Inga Stellmacher,
Laura Victoria Szymkowiak,
Andrea Nist,
Thorsten Stiewe,
Tilman Borggrefe,
Matthias Mann,
Joel P. Mackay,
Marek Bartkuhn (),
Annette Borchers (),
Jie Lan () and
Sandra B. Hake ()
Additional contact information
Andreas Herchenröther: Justus-Liebig University Giessen
Stefanie Gossen: Philipps University Marburg
Tobias Friedrich: Justus-Liebig University Giessen
Alexander Reim: Max-Planck Institute of Biochemistry
Nadine Daus: Justus-Liebig University Giessen
Felix Diegmüller: Justus-Liebig University Giessen
Jörg Leers: Justus-Liebig University Giessen
Hakimeh Moghaddas Sani: University of Sydney
Sarah Gerstner: Philipps University Marburg
Leah Schwarz: Philipps University Marburg
Inga Stellmacher: Justus-Liebig University Giessen
Laura Victoria Szymkowiak: Justus-Liebig University Giessen
Andrea Nist: Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Philipps-University Marburg
Thorsten Stiewe: Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Philipps-University Marburg
Tilman Borggrefe: Justus-Liebig University Giessen
Matthias Mann: Max-Planck Institute of Biochemistry
Joel P. Mackay: University of Sydney
Marek Bartkuhn: Justus-Liebig University Giessen
Annette Borchers: Philipps University Marburg
Jie Lan: Justus-Liebig University Giessen
Sandra B. Hake: Justus-Liebig University Giessen
Nature Communications, 2023, vol. 14, issue 1, 1-20
Abstract:
Abstract Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as a direct histone variant H2A.Z interactor involved in mitosis and craniofacial development. Here, we identify the H2A.Z/PWWP2A-associated protein HMG20A as part of several chromatin-modifying complexes, including NuRD, and show that it localizes to distinct genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis. Our data indicate that craniofacial malformations are caused by defects in neural crest cell (NCC) migration and cartilage formation. These developmental failures are phenocopied in Hmg20a-depleted mESCs, which show inefficient differentiation into NCCs and cardiomyocytes (CM). Consequently, loss of HMG20A, which marks open promoters and enhancers, results in chromatin accessibility changes and a striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and differentiation processes. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and reveal it as a key modulator of intricate developmental transcription programs that guide the differentiation of NCCs and CMs.
Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36114-x
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DOI: 10.1038/s41467-023-36114-x
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