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Genome-wide analysis reveals that Smad3 and JMJD3 HDM co-activate the neural developmental program
Conchi Estarás, Naiara Akizu, Alejandra García, Sergi Beltrán, Xavier de la Cruz, Marian A. Martínez-Balbás


Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFβ pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFβ-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFβ developmental program to proceed.


  • Funding

    This study was supported by the Spanish Ministry of Education and Science [CSD2006-00049 and BFU2009-11527 to M.A.M.-B., and BFU2009-11527 and BIO2006-15557 to X.C.], by Fundaciò La Marató de TV3 [090210 to M.A.M.-B.] and by Consejo Superior de Investigaciones Científicas [200420E578 to X.C.]. C.E. and N.A. were recipients of FPU and I3P (I3P-BPD2005) fellowships, respectively.

  • Competing interests statement

    The authors declare no competing financial interests.

  • Supplementary material

    Supplementary material available online at http://dev.biologists.org/lookup/suppl/doi:10.1242/dev.078345/-/DC1

  • Accepted May 8, 2012.
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