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Allele-specific MMP-3 transcription under in vivo conditions
KTH, School of Biotechnology (BIO), Gene Technology.
2006 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 348, no 3, 1150-1156 p.Article in journal (Refereed) Published
Abstract [en]

A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1 beta, the haplotype containing the 5A-allete was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

Place, publisher, year, edition, pages
2006. Vol. 348, no 3, 1150-1156 p.
Keyword [en]
matrix metalloproteinases, polymorphism, promoter, transcription, inflammation, haplochip, 5a/6a promoter polymorphism, coronary-artery-disease, myocardial-infarction, matrix-metalloproteinase, stromelysin promoter, gene-transcription, heart-disease, atherosclerosis, progression, matrix-metalloproteinase-3
URN: urn:nbn:se:kth:diva-15952DOI: 10.1016/j.bbrc.2006.07.174ISI: 000240166500051ScopusID: 2-s2.0-33747173397OAI: diva2:333994
QC 20100525Available from: 2010-08-05 Created: 2010-08-05Bibliographically approved

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Odeberg, Jacob
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