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

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2681-2691
Number of pages11
JournalDevelopment (Cambridge)
Volume139
Issue number15
DOIs
StatePublished - Aug 2012

Keywords

  • Animals
  • Chick Embryo
  • Developmental Biology/methods
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Green Fluorescent Proteins/metabolism
  • HEK293 Cells
  • Humans
  • Jumonji Domain-Containing Histone Demethylases/metabolism
  • Mice
  • Models, Biological
  • Neurons/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Smad3 Protein/metabolism
  • Spinal Cord/embryology
  • Transforming Growth Factor beta/metabolism

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