Interleukin-6 repression is associated with a distinctive chromatin structure of the gene.
AUTOR(ES)
Armenante, F
RESUMO
Expression of the interleukin-6 (IL-6) gene is usually tightly controlled and may be induced in specific tissues only after treatment with appropriate stimuli. The molecular mechanisms responsible for IL-6 gene repression in specific tissues or cell lines remain poorly defined. In order to address this question we have studied two human breast carcinoma cell lines, MDA-MB-231, in which the IL-6 gene is expressed, and MCF-7, in which it is not. The promoter region of the IL-6 gene was analysed in both cell lines with reference to two different parameters: (i) DNase I hypersensitivity; (ii) the in vivo pattern of DNA-protein interactions. We show herein that the mechanism responsible for silencing IL-6 gene expression in MCF-7 cells most probably involves a modification of chromatin structure, as suggested by a decreased sensitivity of the IL-6 promoter to DNase I relative to the IL-6-expressing cell line MDA-MB-231. Moreover, we show that a 'closed' nucleosomal structure in MCF-7 cells does not inhibit the binding of nuclear proteins to IL-6 gene regulatory sequences in vivo. We suggest, therefore, that, in non-expressing cells, local chromatin remodelling at the proximal promoter is inhibited by negative regulators, as suggested by two specific hallmarks of nuclear factor binding that are not observed in expressing cells: an additional in vivo footprint spanning positions -135/-119 and an additional DNase I hypersensitive site far upstream, around position -1400. Furthermore, a specific factor binding in vitro to the -140/-116 region of the IL-6 promoter is found in MCF-7 cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=148733Documentos Relacionados
- Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene.
- Nuclear factors interacting with an interleukin-6 responsive element of rat alpha 2-macroglobulin gene.
- Rapid detection and sequencing of alleles in the 3' flanking region of the interleukin-6 gene.
- Transcriptional Regulation of the Interleukin-6 Gene of Human Herpesvirus 8 (Kaposi's Sarcoma-Associated Herpesvirus)
- The human haptoglobin gene promoter: interleukin-6-responsive elements interact with a DNA-binding protein induced by interleukin-6