The H2A.Z.1/PWWP2A/NuRD-associated protein HMG20A controls early head and heart developmental transcription programs [HeLa_ChIP_AH]

Specialized 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 HMG20A protein as part of several chromatin-modifying complexes including NuRD, and to localize to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis due to neural crest cell (NCC) and cardiomyocyte (CM) differentiation malfunctions. Such defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and CMs. Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and cardiac differentiation, thereby shedding light on HMG20A-specific developmental defects. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and as a key modulator during NCC and cardiomyocyte differentiation by guiding intricate developmental transcription programs. Overall design: Genomic localisation and influence on transcriptome of HMG20A in Hela Kyoto and in vitro mouse cardiac differentiation