Epigenetic activation of Sox2 gene in the developing vertebrate neural plate

BOUZAS, S.; MARINI, M.; TORRES ZELADA, E.; BUZZI, A. L.; MORALES VICENTE, D. A. ; STROBL MAZZULLA, P.H.

MOLECULAR BIOLOGY OF THE CELL

AMER SOC CELL BIOLOGY

Año: 2016 vol. 27 p. 1921 - 1927

1059-1524

One of the earliest manifestations of neural inductionis onset of expression of the neural marker Sox2,mediated by the activation of the enhancers N-1 and N-2. By using loss andgain-of-function we find that Sox2 expressionrequires the activity of JmjD2A andthe Msk1 kinase, which can respectivelydemethylate the repressive H3K9me3 mark and phosphorylate the activating H3S10(H3S10ph) mark. Bimolecular fluorescence complementation reveals that the adaptorprotein 14-3-3, known to bind to H3S10ph, interacts with JMJD2A and may beinvolved in its recruitment to regulatory regions of Sox2 gene. Chromatin immunoprecipitation reveals dynamic binding ofJMJD2A to the Sox2 promoter and N-1enhancer at the time of neural plate induction. Finally, we show a cleartemporal antagonism on the occupancy of H3K9me3 and H3S10ph modifications atthe promoter of Sox2 locus before and after the neural plate induction. Taken together,we propose a series of epigenetic events necessary for the early activation of theSox2 gene in neural progenitor cells.