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

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.
Mesh Terms:
14-3-3 Proteins, Acetylation, Animals, Cell Line, Chromatin Assembly and Disassembly, Extracellular Signal-Regulated MAP Kinases, Gene Knockout Techniques, Genes, Immediate-Early, Histones, Isoquinolines, MAP Kinase Signaling System, Mice, Nucleosomes, Phosphorylation, Promoter Regions, Genetic, Protein Kinase Inhibitors, Ribosomal Protein S6 Kinases, 90-kDa, Serine, Sulfonamides, Transcription, Genetic
Nucleic Acids Res.
Date: Jun. 01, 2010
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