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Here, we explore whether silencing via promoter DNA methylation plays a role in neural versus neural crest cell lineage decisions. We show that DNA methyltransferase3A (DNMT3A) promotes neural crest specification by directly mediating repression of neural genes like Sox2 and Sox3. DNMT3A is expressed in the neural plate border, and its knockdown causes ectopic Sox2 and Sox3 expression at the expense of neural crest markers. In vivo chromatin immunoprecipitation of neural folds demonstrates that DNMT3A specifically associates with CpG islands in the Sox2 and Sox3 promoter regions, resulting in their repression by methylation. Thus, DNMT3A functions as a molecular switch, repressing neural to favor neural crest cell fate.

DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition