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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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Borghaei RC,Gorski G,Javadi M,Mariah Chambers.

doi

10.1016/j.bbrc.2009.03.002

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

269-73

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)00451-3

journal_volume

382

pub_type

杂志文章

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