rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
14
|
pubmed:dateCreated |
2002-4-1
|
pubmed:abstractText |
Dermo-1 is a multifunctional basic helix-loop-helix (bHLH) transcription factor that has been shown to be a potent negative regulator for gene transcription and apoptosis. To understand the molecular mechanisms that mediate the function of Dermo-1, we generated a series of Dermo-1 mutants and used a MyoD-mediated transcriptional activation model to characterize the roles of its N-terminal, bHLH, and C-terminal structural domains in transcriptional repression. Both the C-terminal and HLH domains of Dermo-1 were essential for its repression of MyoD-mediated transactivation. Dermo-1 repressed, in a dose-dependent fashion, the transactivation activity of myocyte enhancer factor 2 (MEF2), a protein known to cooperate with MyoD in activating E-box-dependent gene expression. Both the N- and C-terminal domains of Dermo-1, but not the bHLH domain, were required for the inhibition of MEF2, suggesting that Dermo-1 inhibits both MyoD- and MEF2-dependent transactivation but through different mechanisms. Dermo-1 interacted directly with MEF2 and selectively repressed the MEF2 transactivation domain. An overall increase of histone acetylation induced by trichostatin A treatment reduced Dermo-1 transcriptional repression activity, suggesting that histone deacetylation is involved in Dermo-1-mediated transcriptional repression. Together, these results suggest that MEF2 is an important target in Dermo-1-mediated transcriptional repression and provide initial evidence of the involvement of histone acetylation in Dermo-1 transcriptional repression.
|
pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MyoD Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Myogenic Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Twist Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Twist2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/myocyte-specific enhancer-binding...,
http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0021-9258
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
5
|
pubmed:volume |
277
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
12310-7
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:11809751-Acetylation,
pubmed-meshheading:11809751-Amino Acid Sequence,
pubmed-meshheading:11809751-Animals,
pubmed-meshheading:11809751-Blotting, Western,
pubmed-meshheading:11809751-Chromatin,
pubmed-meshheading:11809751-DNA, Complementary,
pubmed-meshheading:11809751-DNA-Binding Proteins,
pubmed-meshheading:11809751-Dose-Response Relationship, Drug,
pubmed-meshheading:11809751-Histone Deacetylases,
pubmed-meshheading:11809751-Histones,
pubmed-meshheading:11809751-Hydroxamic Acids,
pubmed-meshheading:11809751-Luciferases,
pubmed-meshheading:11809751-Mice,
pubmed-meshheading:11809751-Models, Biological,
pubmed-meshheading:11809751-Molecular Sequence Data,
pubmed-meshheading:11809751-Mutation,
pubmed-meshheading:11809751-MyoD Protein,
pubmed-meshheading:11809751-Myogenic Regulatory Factors,
pubmed-meshheading:11809751-Point Mutation,
pubmed-meshheading:11809751-Precipitin Tests,
pubmed-meshheading:11809751-Protein Binding,
pubmed-meshheading:11809751-Protein Structure, Tertiary,
pubmed-meshheading:11809751-Repressor Proteins,
pubmed-meshheading:11809751-Sequence Homology, Amino Acid,
pubmed-meshheading:11809751-Transcription, Genetic,
pubmed-meshheading:11809751-Transcription Factors,
pubmed-meshheading:11809751-Transcriptional Activation,
pubmed-meshheading:11809751-Transfection,
pubmed-meshheading:11809751-Twist Transcription Factor
|
pubmed:year |
2002
|
pubmed:articleTitle |
Dermo-1, a multifunctional basic helix-loop-helix protein, represses MyoD transactivation via the HLH domain, MEF2 interaction, and chromatin deacetylation.
|
pubmed:affiliation |
Department of Internal Medicine and the Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|