cAMP-response element-binding protein (CREB) controls MSK1-mediated phosphorylation of histone H3 at the c-fos promoter in vitro.
The rapid induction of the c-fos gene correlates with phosphorylations of histone H3 and HMGN1 by mitogen- and stress-activated protein kinases. We have used a cell-free system to dissect the mechanism by which MSK1 phosphorylates histone H3 within the c-fos chromatin. Here, we show that the reconstituted c-fos chromatin presents a strong barrier to histone H3 phosphorylation by MSK1; however, the activators (serum response factor, Elk-1, cAMP-response element-binding protein (CREB), and ATF1) bound on their cognate sites recruit MSK1 to phosphorylate histone H3 at Ser-10 within the chromatin. This activator-dependent phosphorylation of histone H3 is enhanced by HMGN1 and occurs preferentially near the promoter region. Among the four activators, CREB plays a predominant role in MSK1-mediated phosphorylation of histone H3, and the phosphorylation of Ser-133 in CREB is essential for this process. Mutational analyses of MSK1 show that its N-terminal inhibition domain is critical for the kinase to phosphorylate chromatin-embedded histone H3 in a CREB-dependent manner, indicating the presence of an intricate regulatory network for MSK1-mediated phosphorylation of histone H3.
Shimada
Miho
M
Department of Molecular Biology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495.
Nakadai
Tomoyoshi
T
Department of Molecular Biology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495.
Fukuda
Aya
A
Department of Biochemistry, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
Hisatake
Koji
K
Department of Biochemistry, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan. Electronic address: kojihisa@md.tsukuba.ac.jp.
D002843:Chromatin / Q000737:chemistry; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004252:DNA Mutational Analysis; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D014158:Transcription, Genetic
D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; D016760:Proto-Oncogene Proteins c-fos; D012694:Serine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1