Nucleic Acids Research, Vol 27, Issue 22 4483-4490, Copyright © 1999 by Oxford University Press
F Armenante, M Merola, A Furia, M Tovey and M Palmieri
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.
ARTICLES
Interleukin-6 repression is associated with a distinctive chromatin structure of the gene
Dipartimento di Scienze Neurologiche e della Visione, Sezione di Chimica Biologica, Facolta' di Medicina e Chirurgia, Universita' di Verona, Strada le Grazie 8, 37134 Verona, Italy.
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