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

Hu, Na and Strobl-Mazzulla, Pablo and Sauka-Spengler, Tatjana and Bronner, Marianne E. (2012) DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition. Genes and Development, 26 (21). pp. 2380-2385. ISSN 0890-9369. PMCID PMC3489996. https://resolver.caltech.edu/CaltechAUTHORS:20121102-112018740

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1101/gad.198747.112 DOIArticle
http://genesdev.cshlp.org/content/26/21/2380PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489996/PubMed CentralArticle
ORCID:
AuthorORCID
Strobl-Mazzulla, Pablo0000-0003-0591-6168
Sauka-Spengler, Tatjana0000-0001-9289-0263
Bronner, Marianne E.0000-0003-4274-1862
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.
Funders:
Funding AgencyGrant Number
NIHF31DE021643
NIH5 T32 GM07616
NIHHD037105
NIHDE16459
Subject Keywords:DNMT3A; neural tube; neural crest; Sox2; Sox3
Issue or Number:21
PubMed Central ID:PMC3489996
Record Number:CaltechAUTHORS:20121102-112018740
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20121102-112018740
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35267
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:02 Nov 2012 18:37
Last Modified:09 Mar 2020 13:19

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