NF-KappaB and ZBP-89 Regulate MMP-3 Expression Via a Polymorphic Site in the Promoter

Ruth C. Borghaei, Philadelphia College of Osteopathic Medicine
Grzegorz Gorski, Philadelphia College of Osteopathic Medicine
Masoud Javadi, Philadelphia College of Osteopathic Medicine
Mariah Chambers, Philadelphia College of Osteopathic Medicine

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

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.