Source:http://linkedlifedata.com/resource/pubmed/id/10593968
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
51
|
pubmed:dateCreated |
2000-1-27
|
pubmed:abstractText |
DNA methylation inhibits transcription driven by the collagen alpha2(I) promoter and the 5' end of the gene in transient transfection and in vitro transcription assays. DNA-binding proteins in a unique family of ubiquitously expressed proteins, methylated DNA-binding protein (MDBP)/regulatory factor for X box (RFX), form specific complexes with a sequence overlapping the transcription start site of the collagen alpha2(I) gene. Complex formation increased when the CpG site at +7 base pairs from the transcription start site was methylated. The identity of the protein was demonstrated by co-migration and cross-competition for a characteristic slowly migrating doublet complex formed on MDBP/RFX recognition sequences and the collagen sequences by band shift assays. A RFX1-specific antibody supershifted the collagen DNA-protein complexes. Furthermore, in vitro translated RFX1 protein formed a specific complex with the collagen sequence that was also supershifted with the RFX1 antibody. MDBP/RFX displayed a higher affinity binding to the collagen sequence if the CpG at +7 was mutated in a manner similar to TpG. This same mutation within reporter constructs inhibited transcription in transfection and in vitro transcription assay. These results support the hypothesis that DNA methylation-induced inactivation of collagen alpha2(I) gene transcription is mediated, in part, by increased binding of MDBP/RFX to the first exon in response to methylation in this region.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mbd1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/alpha 2(I) collagen
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
0021-9258
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
17
|
pubmed:volume |
274
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
36649-55
|
pubmed:dateRevised |
2011-11-17
|
pubmed:meshHeading |
pubmed-meshheading:10593968-Animals,
pubmed-meshheading:10593968-Base Sequence,
pubmed-meshheading:10593968-Cells, Cultured,
pubmed-meshheading:10593968-Collagen,
pubmed-meshheading:10593968-Collagen Type I,
pubmed-meshheading:10593968-DNA Methylation,
pubmed-meshheading:10593968-DNA-Binding Proteins,
pubmed-meshheading:10593968-Exons,
pubmed-meshheading:10593968-Fibroblasts,
pubmed-meshheading:10593968-Molecular Sequence Data,
pubmed-meshheading:10593968-Mutation,
pubmed-meshheading:10593968-Promoter Regions, Genetic,
pubmed-meshheading:10593968-Rats,
pubmed-meshheading:10593968-Transcriptional Activation
|
pubmed:year |
1999
|
pubmed:articleTitle |
A methylation-responsive MDBP/RFX site is in the first exon of the collagen alpha2(I) promoter.
|
pubmed:affiliation |
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|