期刊
NUCLEIC ACIDS RESEARCH
卷 38, 期 10, 页码 3196-3208出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq030
关键词
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资金
- Canadian Cancer Society Research Institute [017136]
- Canada Research Chair
- Canadian Cancer Society Research Institute Terry Fox Foundation
- Manitoba Health Research Council
- Canada Foundation for Innovation
- Natural Sciences and Engineering Research Council of Canada [RGPIN/355727-2008]
- University of Manitoba
- Manitoba Medical Service Foundation
- Manitoba Blue Cross
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-kappa B. 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.
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