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Published November 1, 2012 | Supplemental Material + Published
Journal Article Open

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

Abstract

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.

Additional Information

© 2012 by Cold Spring Harbor Laboratory Press. Received June 17, 2012; revised version accepted September 13, 2012. We thank Drs. M. Simoes-Costa and M. Barembaum for helpful discussions. We are grateful to Dr. Yoshio Wakamatsu for kindly providing the Sox2 overexpression construct. This work was supported by F31DE021643 and 5 T32 GM07616 to N.H., and HD037105 and DE16459 to M.E.B.

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Published - Genes_Dev.-2012-Hu-2380-5.pdf

Supplemental Material - Supplemental_Info.pdf

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