Title:
Transcription factor ATF-3 regulates allele variation phenotypes of the
human SLC11A1 gene
Languages of Item:
English
Abstract:
Genetic polymorphisms in the human solute carrier family 11 member 1
(SLC11A1) gene predispose to susceptibility to infectious/inflammatory
diseases and cancer. Human susceptibility to these diseases exhibits
allelic association with a polymorphic regulatory Z-DNA-forming
microsatellite of a (GT/AC)n repeat. The carriage of different alleles
may influence chromatin remodeling and accessibility by transcription
factors. Of particular importance is the binding site for the Activating
Protein 1 (AP-1) elements, (ATF-3 and c-Jun), adjacent to the 5’
sequence of the Z-DNA-forming polymorphism. The aim of the study was to
characterize the transcriptional mechanisms controlling different
alleles of SLC11A1 expression by ATF-3 and c-Jun. Allele 2,
[T(GT)(5)AC(GT)(5)AC(GT)(10)GGCAGA(G)(6)], and Allele 3,
[T(GT)(5)AC(GT)(5)AC(GT)(9)GGCAGA(G)(6)], were subcloned into the
PGL2Basic vector. Transient transfections of THP-1 cells with the
constructs, in the presence or absence of pATF-3 were preformed.
Luciferase expression was determined. To document the recruitment of
ATF-3 and c-Jun, to the polymorphic promoter alleles in vivo, we
performed ChIP assays with transient transfected THP-1 cells treated
with or without lipopolyssacharides. Our data documented that ATF-3
suppresses the transcriptional activation of Allele-3, and this
suppression is enhanced in the presence of lipopolyssacharides. Our
findings suggest that ATF-3 and c-Jun may influence heritable variation
in SLC11A1-dependent innate resistance to infection and inflammation
both within and between populations.
Authors:
Taka, Styliani
Gazouli, Maria
Politis, Panagotis K.
Pappa,
Kalliopi I.
Anagnou, Nicholas P.
Journal:
Current Molecular Biology Reports
Publisher:
Springer-Verlag
Keywords:
SLC11A1; ATF-3; c-Jun; Transcriptional regulation; Innate resistance
Official URL (Publisher):
DOI:
10.1007/s11033-012-2289-1
