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XB-ART-59531
Nat Commun 2023 Jan 28;141:472. doi: 10.1038/s41467-023-36114-x.
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The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs.

Herchenröther A , Gossen S , Friedrich T , Reim A , Daus N , Diegmüller F , Leers J , Sani HM , Gerstner S , Schwarz L , Stellmacher I , Szymkowiak LV , Nist A , Stiewe T , Borggrefe T , Mann M , Mackay JP , Bartkuhn M , Borchers A , Lan J , Hake SB .


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.

PubMed ID: 36709316
PMC ID: PMC9884267
Article link: Nat Commun


Species referenced: Xenopus laevis
Genes referenced: bend3 brd2 cdh2 cdk2ap1 cdk2ap2 chd3 chd4 eif4h gata4 gatad2a gatad2b gse1 h2ac21 h2az1 h2az2 hdac1 hdac2 hmg20a hprt1 isyna1 itk l3mbtl3 mbd2 mbd3 mta1 mta2 myh6 phf14 phf21a pwwp2a rai1 rbbp4 rbbp7 rcor1 rcor3 rpe rpl11 tcf20 tead1 twist1 znf219 znf512b
GO keywords: chromatin binding [+]
Morpholinos: hmg20a MO1

Disease Ontology terms: autism spectrum disorder [+]
Phenotypes: Xla Wt + hmg20a MO (Fig 4.A r2c1-3) [+]

Article Images: [+] show captions
References [+] :
Achilleos, Neural crest stem cells: discovery, properties and potential for therapy. 2012, Pubmed