Molecular Biology Reports

, Volume 40, Issue 3, pp 2263–2271 | Cite as

Transcription factor ATF-3 regulates allele variation phenotypes of the human SLC11A1 gene

  • Styliani Taka
  • Maria Gazouli
  • Panagotis K. Politis
  • Kalliopi I. Pappa
  • Nicholas P. Anagnou
Article

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)5AC(GT)5AC(GT)10GGCAGA(G)6], and Allele 3, [T(GT)5AC(GT)5AC(GT)9GGCAGA(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.

Keywords

SLC11A1 ATF-3 c-Jun Transcriptional regulation Innate resistance 

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Styliani Taka
    • 1
  • Maria Gazouli
    • 1
  • Panagotis K. Politis
    • 2
  • Kalliopi I. Pappa
    • 3
  • Nicholas P. Anagnou
    • 1
    • 3
  1. 1.Laboratory of BiologyUniversity of Athens School of MedicineAthensGreece
  2. 2.Histology Laboratory, Centre of Basic Research IBiomedical Research Foundation, Academy of Athens (BRFAA)AthensGreece
  3. 3.Cell and Gene Therapy Laboratory, Centre of Basic ResearchBiomedical Research Foundation, Academy of Athens (BRFAA)AthensGreece

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