Linked Life Data

11238113

Source:http://linkedlifedata.com/resource/pubmed/id/11238113

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-3-12
pubmed:abstractText
Genetically controlled variation in alpha2beta1 expression by human blood platelets was previously described. Sixty-two haplotype sequences corresponding to the proximal 5' regulatory region (-1096 to +1) of the alpha2 gene were compared, and a dimorphic sequence -52C>T was identified that is located precisely between 2 tandem Sp1/Sp3 binding elements previously shown to be absolutely required for transcriptional activity of this gene in epithelial cell lines and the erythroleukemic cell line K562. The gene frequency of -52T in a random Caucasian population is approximately 0.35, and the expression of -52T correlates directly with reduced densities of platelet alpha2beta1. In mobility shift analyses, the -52T substitution attenuates complex formation with both Sp1 and Sp3. When transfected into the erythroleukemia cell line Dami, promoter-luciferase constructs bearing the -52T sequence exhibit a 5-fold decrease in activity relative to the -52C construct. In transfected CHRF-288-11 megakaryocytic cells, the corresponding activity decreases by 10-fold. The -52T sequence appears to be in linkage disequilibrium with the previously defined allele A3 (807C; HPA-5b), known to be associated with diminished expression of platelet alpha2beta1. In summary, a natural dimorphism has been identified within the proximal 5' regulatory region of the human integrin alpha2 gene that is responsible for decreased expression levels of the integrin alpha2beta1 on blood platelets through a mechanism that is probably mediated by the nuclear regulatory proteins Sp1 and Sp3.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1721-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11238113-5' Untranslated Regions, pubmed-meshheading:11238113-Alleles, pubmed-meshheading:11238113-Antigens, CD, pubmed-meshheading:11238113-Blood Platelets, pubmed-meshheading:11238113-DNA-Binding Proteins, pubmed-meshheading:11238113-Down-Regulation, pubmed-meshheading:11238113-Gene Expression Regulation, pubmed-meshheading:11238113-Genes, Regulator, pubmed-meshheading:11238113-Humans, pubmed-meshheading:11238113-Integrin alpha2, pubmed-meshheading:11238113-Integrins, pubmed-meshheading:11238113-Leukocytes, Mononuclear, pubmed-meshheading:11238113-Linkage Disequilibrium, pubmed-meshheading:11238113-Pregnancy Proteins, pubmed-meshheading:11238113-Protein Binding, pubmed-meshheading:11238113-Receptors, Collagen, pubmed-meshheading:11238113-Sp1 Transcription Factor, pubmed-meshheading:11238113-Transcription, Genetic
pubmed:year
2001
pubmed:articleTitle
Allele-dependent transcriptional regulation of the human integrin alpha2 gene.
pubmed:affiliation
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis of the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't