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-kB 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 2 kb of the MMP-3 promoter showed that NF-kB 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-kB 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.
| Original language | American English |
|---|---|
| Journal | Biochemical and biophysical research communications |
| Volume | 382 |
| State | Published - Jan 1 2009 |
Keywords
- Matrix metalloproteinase
- NF-kB
- Polymorphism
- Stromelysin-1
- Transcription factor
- ZBP-89
- ZNF148
- immunoglobulin enhancer binding protein
- stromelysin
- unclassified drug
- zinc binding protein
- zinc binding protein 89
- DNA binding protein
- ZNF148 protein
- human
- animal cell
- article
- binding site
- cell strain COS1
- chromatin immunoprecipitation
- controlled study
- enzyme regulation
- genetic polymorphism
- genetic transcription
- genetic transfection
- human cell
- nonhuman
- plasmid
- priority journal
- promoter region
- protein binding
- protein expression
- regulatory mechanism
- animal
- Cercopithecus
- gene expression regulation
- genetics
- metabolism
- Animals
- Cercopithecus aethiops
- COS Cells
- DNA-Binding Proteins
- Humans
- Matrix Metalloproteinase 3
- NF-kappa B
- Genetic
- Promoter Regions
- Transcription Factors
- Transcription
Disciplines
- Genetics and Genomics