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.
Drobic
Bojan
B
Department of Immunology, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Manitoba R3E 0V9, Canada.
Pérez-Cadahía
Beatriz
B
Yu
Jenny
J
Kung
Sam Kam-Pun
SK
Davie
James R
JR
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