title: DNA methyltransferase 3B regulates duration of neural crest production via repression of Sox10.
abstract: 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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 and.
authors.forename: Na
authors.initials: N
authors.lastname: Hu
authors.affiliation: Laboratorio de biología del desarrollo, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), Chascomús, 7130 Buenos Aires, Argentina.
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Strobl-Mazzulla
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 and.
authors.forename: Marcos
authors.initials: M
authors.lastname: Simoes-Costa
authors.affiliation: Laboratorio de biología del desarrollo, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), Chascomús, 7130 Buenos Aires, Argentina.
authors.forename: Estefania
authors.initials: E
authors.lastname: Sánchez-Vásquez
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 and mbronner@caltech.edu.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
mesh_terms: D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000502:physiology*; D018274:Electroporation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055757:SOXE Transcription Factors / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D055757:SOXE Transcription Factors; D000097584:DNA Methyltransferase 3B
keywords: DNA methylation; DNMT3B; Sox10; epigenetic; neural crest