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DNA methyltransferase 3B regulates duration of neural crest production via repression of Sox10

Hu, Na and Strobl-Mazzulla, Pablo H. and Simões-Costa, Marcos and Sánchez-Vásquez, Estefania and Bronner, Marianne E. (2014) DNA methyltransferase 3B regulates duration of neural crest production via repression of Sox10. Proceedings of the National Academy of Sciences of the United States of America, 111 (50). pp. 17911-17916. ISSN 0027-8424. PMCID PMC4273375. doi:10.1073/pnas.1318408111.

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Neural crest stem cells arise within the central nervous system but then undergo an epithelial-to-mesenchymal transition to migrate away and contribute to the peripheral nervous system and craniofacial skeleton. Here we show that DNA methyltransferase 3B (DNMT3B) is responsible for the loss of competence of dorsal neural tube cells to generate emigrating neural crest cells. DNMT3B knockdown results in up-regulation of neural crest markers, prolonged neural crest emigration, and subsequent precocious neuronal differentiation of the trigeminal ganglion. We find that DNMT3B binds to the promoter of Sox10, known to be important for neural crest emigration and lineage acquisition. Bisulfite sequencing further reveals methylation of the Sox10 promoter region upon cessation of emigration in normal embryos, whereas this mark is reduced after DNMT3B loss. Taken together, these results reveal the importance of DNA methylation in regulating the ability of neural tube cells to produce neural crest cells and the timing of peripheral neuron differentiation.

Item Type:Article
Related URLs:
URLURL TypeDescription DOIArticle Material CentralArticle
Strobl-Mazzulla, Pablo H.0000-0003-0591-6168
Simões-Costa, Marcos0000-0003-1452-7068
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2014 National Academy of Sciences. Published online before print December 1, 2014, doi:10.1073/pnas.1318408111 PNAS December 1, 2014 Edited by Joseph R. Ecker, Howard Hughes Medical Institute and The Salk Institute for Biological Studies, La Jolla, CA, and approved November 5, 2014 (received for review September 30, 2013) We thank Drs. T. Sauka-Spengler and M. Barembaum for helpful discussions. This work was supported by Grants F31DE021643 and Q:10 5 T32 GM07616 (to N.H.) and HD037105 and DE16459 (to M.E.B.). Author contributions: N.H., P.H.S.-M., M.S.-C., and M.E.B. designed research; N.H., P.H.S.-M., M.S.-C., and E.S.-V. performed research; N.H., P.H.S.-M., M.S.-C., E.S.-V., and M.E.B. analyzed data; and N.H., P.H.S.-M., and M.E.B. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. N.H. and P.H.S.-M. contributed equally to this work. This article contains supporting information online at
Funding AgencyGrant Number
NIH5 T32 GM07616
Subject Keywords:neural crest ; epigenetic ; DNMT3B ; Sox10 ; DNA methylation
Issue or Number:50
PubMed Central ID:PMC4273375
Record Number:CaltechAUTHORS:20141114-094819602
Persistent URL:
Official Citation:Na Hu, Pablo H. Strobl-Mazzulla, Marcos Simoes-Costa, Estefania Sánchez-Vásquez, and Marianne E. Bronner DNA methyltransferase 3B regulates duration of neural crest production via repression of Sox10 PNAS 2014 111 (50) 17911-17916; published ahead of print December 1, 2014, doi:10.1073/pnas.1318408111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51757
Deposited By: Katherine Johnson
Deposited On:03 Dec 2014 21:14
Last Modified:10 Nov 2021 19:15

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