Source:http://linkedlifedata.com/resource/pubmed/id/12821655
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
37
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pubmed:dateCreated |
2003-9-8
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pubmed:abstractText |
Localization of transcription regulatory proteins in the nucleus is dynamically regulated, and may alter nucleoplasmic concentrations and/or assembly of multimolecular transcription regulatory complexes, which ultimately regulate gene expression. Since growth hormone (GH) regulates multiple transcription factors including C/EBP beta, the effect of GH on the subcellular localization of C/EBP beta was examined in 3T3-F442A preadipocytes. Indirect immunofluorescence shows that C/EBP beta is diffusely distributed in nuclei of quiescent cells. Within 5 min of GH treatment, the diffuse pattern dramatically becomes punctate. The relocalization of C/EBP beta coincides with DAPI staining of heterochromatin. Further, C/EBP beta and heterochromatin protein (HP)-1 alpha colocalize in the nucleus, consistent with localization of C/EBP beta to pericentromeric heterochromatin. In contrast, C/EBP delta exhibits a diffuse distribution in the nucleus that is not modified by GH treatment. C/EBP beta is rapidly and transiently phosphorylated on a conserved MAPK consensus site in response to GH (Piwien-Pilipuk, G., MacDougald, O. A., and Schwartz, J. (2002) J. Biol. Chem. 277, 44557-44565). Indirect immunofluorescence using antibodies specific for C/EBP beta phosphorylated on the conserved MAPK site shows that GH also rapidly induces a punctate pattern of staining for the phosphorylated C/EBP beta. In addition, phosphorylated C/EBP beta colocalizes to pericentromeric heterochromatin. The satellite DNA present in heterochromatin contains multiple C/EBP binding sites. DNA binding analysis shows that C/EBP beta, C/EBP delta, and C/EBP alpha (p42 and p30 forms) can bind to satellite DNA as homo- or heterocomplexes in vitro. Importantly, GH rapidly and transiently increases binding of endogenous C/EBP beta from 3T3-F442A cells to satellite DNA. Further, the GH-promoted nuclear relocalization of C/EBP beta to pericentromeric heterochromatin was prevented by the MEK inhibitor U0126. This observation suggests that GH-dependent MAPK activation plays a role in the regulation of nuclear relocalization of C/EBP beta. Nuclear redistribution introduces a new level of transcriptional regulation in GH action, since GH-mediated phosphorylation and nuclear redistribution of C/EBP beta may be coordinated to achieve spatial-temporal control of gene expression.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Satellite,
http://linkedlifedata.com/resource/pubmed/chemical/Heterochromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Human Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35668-77
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12821655-3T3 Cells,
pubmed-meshheading:12821655-Adipocytes,
pubmed-meshheading:12821655-Animals,
pubmed-meshheading:12821655-Binding Sites,
pubmed-meshheading:12821655-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:12821655-Cell Cycle,
pubmed-meshheading:12821655-Cell Differentiation,
pubmed-meshheading:12821655-Cell Nucleus,
pubmed-meshheading:12821655-DNA, Satellite,
pubmed-meshheading:12821655-Heterochromatin,
pubmed-meshheading:12821655-Human Growth Hormone,
pubmed-meshheading:12821655-Mice,
pubmed-meshheading:12821655-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12821655-Phosphorylation
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pubmed:year |
2003
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pubmed:articleTitle |
Subnuclear localization of C/EBP beta is regulated by growth hormone and dependent on MAPK.
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pubmed:affiliation |
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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