Source:http://linkedlifedata.com/resource/pubmed/id/19776015
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
47
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pubmed:dateCreated |
2009-11-16
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pubmed:abstractText |
Changes in the environment of a cell precipitate extracellular signals and sequential cascades of protein modification and elicit nuclear transcriptional responses. However, the functional links between intracellular signaling-dependent gene regulation and epigenetic regulation by chromatin-modifying proteins within the nucleus are largely unknown. Here, we describe novel epigenetic regulation by MAPK cascades that modulate formation of an ATP-dependent chromatin remodeling complex, WINAC (WSTF Including Nucleosome Assembly Complex), an SWI/SNF-type complex containing Williams syndrome transcription factor (WSTF). WSTF, a specific component of two chromatin remodeling complexes (SWI/SNF-type WINAC and ISWI-type WICH), was phosphorylated by the stimulation of MAPK cascades in vitro and in vivo. Ser-158 residue in the WAC (WSTF/Acf1/cbpq46) domain, located close to the N terminus of WSTF, was identified as a major phosphorylation target. Using biochemical analysis of a WSTF mutant (WSTF-S158A) stably expressing cell line, the phosphorylation of this residue (Ser-158) was found to be essential for maintaining the association between WSTF and core BAF complex components, thereby maintaining the ATPase activity of WINAC. WINAC-dependent transcriptional regulation of vitamin D receptor was consequently impaired by this WSTF mutation, but the recovery from DNA damage mediated by WICH was not impaired. Our results suggest that WSTF serves as a nuclear sensor of the extracellular signals to fine-tune the chromatin remodeling activity of WINAC. WINAC mediates a previously unknown MAPK-dependent step in epigenetic regulation, and this MAPK-dependent switching mechanism between the two functionally distinct WSTF-containing complexes might underlie the diverse functions of WSTF in various nuclear events.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1083-351X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
20
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
32472-82
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pubmed:dateRevised |
2011-3-3
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pubmed:meshHeading |
pubmed-meshheading:19776015-Animals,
pubmed-meshheading:19776015-Cell Line,
pubmed-meshheading:19776015-Cell Line, Tumor,
pubmed-meshheading:19776015-Chromatin,
pubmed-meshheading:19776015-DNA Damage,
pubmed-meshheading:19776015-Epigenesis, Genetic,
pubmed-meshheading:19776015-Gene Expression Regulation,
pubmed-meshheading:19776015-Humans,
pubmed-meshheading:19776015-MAP Kinase Signaling System,
pubmed-meshheading:19776015-Mice,
pubmed-meshheading:19776015-Mice, Transgenic,
pubmed-meshheading:19776015-Mutation,
pubmed-meshheading:19776015-Phosphorylation,
pubmed-meshheading:19776015-Protein Structure, Tertiary,
pubmed-meshheading:19776015-Transcription Factors
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pubmed:year |
2009
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pubmed:articleTitle |
Phosphorylation of Williams syndrome transcription factor by MAPK induces a switching between two distinct chromatin remodeling complexes.
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pubmed:affiliation |
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
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pubmed:publicationType |
Journal Article
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