Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex

Nucleic Acids Res. 2010 Jun;38(10):3196-208. doi: 10.1093/nar/gkq030. Epub 2010 Feb 3.


Upon activation of the ERK and p38 MAPK pathways, the MSK1/2-mediated nucleosomal response, including H3 phosphorylation at serine 28 or 10, is coupled with the induction of immediate-early (IE) gene transcription. The outcome of this response, varying with the stimuli and cellular contexts, ranges from neoplastic transformation to neuronal synaptic plasticity. Here, we used sequential co-immunoprecipitation assays and sequential chromatin immunoprecipitation (ChIP) assays on mouse fibroblast 10T1/2 and MSK1 knockdown 10T1/2 cells to show that H3 serine 28 and 10 phosphorylation leads to promoter remodeling. MSK1, in complexes with phospho-serine adaptor 14-3-3 proteins and BRG1 the ATPase subunit of the SWI/SNF remodeler, is recruited to the promoter of target genes by transcription factors such as Elk-1 or NF-kappaB. Following MSK1-mediated H3 phosphorylation, BRG1 associates with the promoter of target genes via 14-3-3 proteins, which act as scaffolds. The recruited SWI/SNF remodels nucleosomes at the promoter of IE genes enabling the binding of transcription factors like JUN and the onset of transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Acetylation
  • Animals
  • Cell Line
  • Chromatin Assembly and Disassembly*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Knockout Techniques
  • Genes, Immediate-Early*
  • Histones / chemistry
  • Histones / metabolism*
  • Isoquinolines / pharmacology
  • MAP Kinase Signaling System
  • Mice
  • Nucleosomes / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic*
  • Protein Kinase Inhibitors / pharmacology
  • Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Serine / metabolism
  • Sulfonamides / pharmacology
  • Transcription, Genetic


  • 14-3-3 Proteins
  • Histones
  • Isoquinolines
  • Nucleosomes
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Serine
  • Ribosomal Protein S6 Kinases, 90-kDa
  • mitogen and stress-activated protein kinase 1
  • Extracellular Signal-Regulated MAP Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide