Epigenetic activation of Sox2 gene in the developing vertebrate neural plate.
One of the earliest manifestations of neural induction is onset of expression of the neural marker Sox2, mediated by the activation of the enhancers N1 and N2. By using loss and gain of function, we find that Sox2 expression requires the activity of JmjD2A and the Msk1 kinase, which can respectively demethylate the repressive H3K9me3 mark and phosphorylate the activating H3S10 (H3S10ph) mark. Bimolecular fluorescence complementation reveals that the adaptor protein 14-3-3, known to bind to H3S10ph, interacts with JMJD2A and may be involved in its recruitment to regulatory regions of the Sox2 gene. Chromatin immunoprecipitation reveals dynamic binding of JMJD2A to the Sox2 promoter and N-1 enhancer at the time of neural plate induction. Finally, we show a clear temporal antagonism on the occupancy of H3K9me3 and H3S10ph modifications at the promoter of the Sox2 locus before and after the neural plate induction. Taken together, our results propose a series of epigenetic events necessary for the early activation of the Sox2 gene in neural progenitor cells.
Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina.
Santiago O
SO
Bouzas
Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina.
Melisa S
MS
Marini
Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina.
Eliana
E
Torres Zelada
Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina.
Ailín L
AL
Buzzi
Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina.
David A
DA
Morales Vicente
Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina strobl@intech.gov.ar.
Pablo H
PH
Strobl-Mazzulla
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D047108:Embryonic Development / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D057890:Epigenomics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D054258:Neural Plate / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D048948:14-3-3 Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1