화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.351, No.3, 777-783, 2006
Allele-specific chromatin remodeling of the tumor necrosis factor-alpha promoter
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-kappa B 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 1 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-kappa B to the TNF-alpha promoter is associated with allele-specific remodeling of chromatin structure. (c) 2006 Elsevier Inc. All rights reserved.