| Autor: |
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, Sandra B. Hake |
| Rok vydání: |
2022 |
| Popis: |
/SummarySpecialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial 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 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 defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and cardiomyocytes (CMs). Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial- mesenchymal transition (EMT) and cardiac differentiation, thereby providing insights into the regulatory circuits controlled by HMG20A. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and reveal it as a key modulator of the intricate developmental transcription programs that guide NCC and cardiomyocyte differentiation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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