
Precise regulation of chromatin plasticity during development is of critical importance. This study identifies the H2A.Z- and PWWP2A-associated protein HMG20A as part of several chromatin-modifying complexes, including NuRD, and shows that it localizes to distinct genomic regulatory regions. Its ablation causes severe head, craniofacial, and heart developmental defects in Xenopus laevis, caused by defects in neural crest cell (NCC) migration and cartilage formation. These effects are reproduced in Hmg20a-depleted mESCs, that exhibit inefficient differentiation to NCCs and cardiomyocytes (CM). 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. Our findings reveal that HMG20A is part of H2A.Z-/PWWP2A-/NuRD-complexes and a key modulator of developmental transcription programs that guide the differentiation of NCCs and CMs.
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