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- Title
Effects of genetic variation on chromatin structure and the transcriptional machinery: analysis of the IL6 gene locus.
- Authors
Smith, A J P; Zheng, D; Palmen, J; Pang, D X; Woo, P; Humphries, S E
- Abstract
The presence of functional regulatory polymorphism at the interleukin 6 (IL6) locus is uncertain, with many conflicting in vitro findings. To examine the in vivo effect of the three putative functional IL6 promoter variants, −174G>C, −572G>C and −6331T>C, two complementary techniques, allele-specific chromatin immunoprecipitation and allele-specific formaldehyde-assisted isolation of regulatory elements, were carried out using unrelated lymphoblast cell lines of known genotype. There were no allele-specific effects for all three single-nucleotide polymorphisms (SNPs) under basal conditions. Upon IL-1β stimulation, however, allele-specific effects were seen for the −6331 allele, which showed both increased RNA polymerase II loading (56%, P=0.001) and increased open chromatin (59%, P=0.004) for the T allele, which is in line with previous reports of this SNP and the effects from acute inflammation. These studies highlight the importance of examining chromatin under different environmental conditions when studying the functionality of regulatory polymorphisms.
- Subjects
MOLECULAR structure of chromatin; GENETIC transcription; INTERLEUKIN-6; IMMUNOPRECIPITATION; SINGLE nucleotide polymorphisms; RNA polymerases
- Publication
Genes & Immunity, 2012, Vol 13, Issue 7, p583
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2012.32