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

STROBL MAZZULLA, P.H.; HU, N.; SIMOES-COSTA, M.; SÁNCHEZ VÁSQUEZ, E.; BRONNER, M.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2014 vol. 111 p. 17911 - 17926

0027-8424

Neural crest stem cells arise within the central nervous system (CNS) 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), expressed in the dorsal neural tube, influences the time during which the CNS produces emigrating neural crest cells. Loss of DNMT3B results in upregulation of neural crest markers and extends the time during which neural tube cells are competent to generate emigrating neural crest cells. Later, this results in precocious neuronal differentiation of the trigeminal ganglion. Chromatin immunoprecipitation shows that DNMT3B binds to the promoter of neural crest gene Sox10, known to be important for emigration and lineage acquisition. Bisulfite sequencing reveals methylation of the Sox10 promoter region upon cessation of neural crest emigration, and this mark is reduced after DNMT3B loss. Our results suggest an important role for DNA methylation in regulating the duration of neural crest production by the neural tube and the timing of peripheral neuron differentiation.