Allele-specific Chromatin Remodeling of the Tumor Necrosis Factor-alpha Promoter.
From: Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden.
Biochemical and biophysical research communications
- Publish Date: Dec 2006
- ISSN: 0006-291X
- Volume: 351
- Issue: 3
- Pages: 777-83
- Medium: Print
- Language: English
- Citation (JAMA): Skoog Tiina, Hamsten Anders, Eriksson Per, et al. Allele-specific Chromatin Remodeling of the Tumor Necrosis Factor-alpha Promoter.. Biochem. Biophys. Res. Commun. Dec 2006;351:777-83
Abstract
The -863 C/A polymorphism in the tumor necrosis factor-alpha (TNF-alpha) promoter has been suggested to influence TNF-alpha expression. Here we elucidated the molecular mechanisms underlying the allele-specific regulation of TNF-alpha gene expression under basal and LPS-stimulated conditions in THP-1 cells and in human primary macrophages. We show that the binding of two NF-kappaB complexes, the p50/p50 homodimer and the p50/p65 heterodimer, was upregulated upon LPS stimulation. Both complexes bound to the C-allele whereas the A-allele only bound the p50/p65 complex. Two DNase I hypersensitive sites appeared in the TNF-alpha promoter after LPS stimulation of THP-1 cells. DNase I hypersensitivity of the TNF-alpha promoter was also analyzed in human monocytes prepared from individuals of different -863C/A genotype. Hypersensitivity was increased in the promoter harboring the mutant A-allele, particularly after LPS stimulation. In summary, binding of transcription factor NF-kappaB to the TNF-alpha promoter is associated with allele-specific remodeling of chromatin structure.
Mesh Headings (Keywords): Alleles, Cells, Cultured, Chromatin Assembly and Disassembly, Humans, Lipopolysaccharides, Monocytes, Polymorphism, Single Nucleotide, Promoter Regions (Genetics), Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 17084384
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.