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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-9-1
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pubmed:abstractText |
The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting that P-TEFb is an essential factor for cardiac myocyte function and development. Here, we present evidence that P-TEFb selectively activates transcription mediated by the myocyte enhancer factor 2 (MEF2) family of transcription factors, key regulatory factors for myocyte development. Knockdown of endogenous cyclin T1 in murine C2C12 cells abolishes MEF2-dependent reporter gene expression as well as transcription of endogenous MEF2 target genes, whereas overexpression of P-TEFb enhances MEF2-dependent transcription. P-TEFb interacts with MEF2 both in vitro and in vivo. Activation of MEF2-dependent transcription induced by serum starvation is mediated by a rapid dissociation of P-TEFb from its inhibitory subunit, HEXIM1, and a subsequent recruitment of P-TEFb to MEF2 binding sites in the promoter region of MEF2 target genes. These results indicate that recruitment of P-TEFb is a critical step for stimulation of MEF2-dependent transcription, therefore providing a fundamentally important regulatory mechanism underlying the transcriptional program in muscle cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCNT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin T,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 4,
http://linkedlifedata.com/resource/pubmed/chemical/Hexim1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Myogenic Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/NR4A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nr4a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nr4a1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Positive Transcriptional...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Steroid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/myocyte-specific enhancer-binding...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1089-8638
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
382
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
275-87
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pubmed:dateRevised |
2011-6-1
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pubmed:meshHeading |
pubmed-meshheading:18662700-Animals,
pubmed-meshheading:18662700-Cells, Cultured,
pubmed-meshheading:18662700-Cyclin T,
pubmed-meshheading:18662700-Cyclin-Dependent Kinase 9,
pubmed-meshheading:18662700-Cyclins,
pubmed-meshheading:18662700-DNA-Binding Proteins,
pubmed-meshheading:18662700-Gene Expression Regulation,
pubmed-meshheading:18662700-Genes, Reporter,
pubmed-meshheading:18662700-Glucose Transporter Type 4,
pubmed-meshheading:18662700-HeLa Cells,
pubmed-meshheading:18662700-Humans,
pubmed-meshheading:18662700-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:18662700-Mice,
pubmed-meshheading:18662700-Muscle, Skeletal,
pubmed-meshheading:18662700-Muscle Cells,
pubmed-meshheading:18662700-Myogenic Regulatory Factors,
pubmed-meshheading:18662700-Nuclear Receptor Subfamily 4, Group A, Member 1,
pubmed-meshheading:18662700-Positive Transcriptional Elongation Factor B,
pubmed-meshheading:18662700-Promoter Regions, Genetic,
pubmed-meshheading:18662700-RNA, Small Interfering,
pubmed-meshheading:18662700-Rats,
pubmed-meshheading:18662700-Receptors, Steroid,
pubmed-meshheading:18662700-Transcription, Genetic,
pubmed-meshheading:18662700-Transcription Factors
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pubmed:year |
2008
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pubmed:articleTitle |
The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2.
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pubmed:affiliation |
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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