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.
Department of Immunology, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Manitoba R3E 0V9, Canada.
Bojan
B
Drobic
Beatriz
B
Pérez-Cadahía
Jenny
J
Yu
Sam Kam-Pun
SK
Kung
James R
JR
Davie
D048948:14-3-3 Proteins / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055786:Gene Knockout Techniques; D017781:Genes, Immediate-Early; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic
D048948:14-3-3 Proteins; D006657:Histones; D007546:Isoquinolines; D009707:Nucleosomes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D012694:Serine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048049:Extracellular Signal-Regulated MAP Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide