title: NF-kappaB and ZBP-89 regulate MMP-3 expression via a polymorphic site in the promoter.
abstract: A 5T/6T polymorphism in the human MMP-3 promoter affects gene expression and impacts the risk and/or severity of various pathological conditions. Chromatin immunoprecipitation (ChIP) in human fibroblasts homozygous for the 6T site demonstrate that it is bound by NF-kappaB and ZBP-89 transcription factors in its native chromatin. ChIP in COS-1 cells transfected with plasmids containing the 5T and 6T sites in the context of 2kb of the MMP-3 promoter showed that NF-kappaB p50 binds preferentially to the 6T site, while more ZBP-89 binding is detected to the 5T site. Over-expressed ZBP-89 increased transcription from the 5T promoter but not from the 6T, while NF-kappaB decreased transcription from both promoters, even in the presence of excess ZBP-89. A model is suggested in which the physiological impact of the polymorphism is dependent on the relative levels and activities of these competing factors in various cell types and conditions.
authors.affiliation: Dept. of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, Philadelphia, PA 19131, USA. ruthb@pcom.edu
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Borghaei
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Gorski
authors.forename: Masoud
authors.initials: M
authors.lastname: Javadi
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D014157:Transcription Factors; C110951:ZNF148 protein, human; D019278:Matrix Metalloproteinase 3