NF-KappaB and ZBP-89 Regulate MMP-3 Expression Via a Polymorphic Site in the Promoter
This article was published in Biochemical and Biophysical Research Communications, Volume 382, Issue 2, 1 May 2009, Pages 269–273.
The published version is available at http://dx.doi.org/10.1016%2Fj.bbrc.2009.03.002
Copyright © 2009 Elsevier Inc.
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.