A chromatin-modifying function of JNK during stem cell differentiation

Nat Genet. 2011 Dec 18;44(1):94-100. doi: 10.1038/ng.1036.


Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH(2)-terminal kinase (JNK) pathway exemplifies one subgroup of the mitogen-activated protein (MAP) kinases, which, besides having established functions in stress response, also contribute to development by an unknown mechanism. We show by genome-wide location analysis that JNK binds to a large set of active promoters during the differentiation of stem cells into neurons. JNK-bound promoters are enriched with binding motifs for the transcription factor NF-Y but not for AP-1. NF-Y occupies these predicted sites, and overexpression of dominant-negative NF-YA reduces the JNK presence on chromatin. We find that histone H3 Ser10 (H3S10) is a substrate for JNK, and JNK-bound promoters are enriched for H3S10 phosphorylation. Inhibition of JNK signaling in post-mitotic neurons reduces phosphorylation at H3S10 and the expression of target genes. These results establish MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Binding Factor / metabolism
  • Cell Differentiation*
  • Chromatin / metabolism*
  • Embryonic Stem Cells
  • Gene Expression Regulation
  • MAP Kinase Kinase 4 / metabolism*
  • MAP Kinase Signaling System / genetics
  • Mice
  • Neural Stem Cells
  • Neurons / physiology
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Stem Cells
  • Up-Regulation


  • CCAAT-Binding Factor
  • Chromatin
  • nuclear factor Y
  • MAP Kinase Kinase 4

Associated data

  • GEO/GSE25533