A repressor in the proximal human inducible nitric oxide synthase promoter modulates transcriptional activation

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Alena PanceJean-François Jeannin

Abstract

The human inducible nitric oxide synthase (iNOS or NOSII) gene is regulated through an extended and complex promoter. In this study, the transcriptional regulation of human NOSII is investigated in the human colon cell line HCT-8R. Stimulation with a cytokine mix (interferon-gamma, interleukin 1-beta, and tumor necrosis factor alpha) induces NOSII mRNA accumulation, as well as promoter activity in these cells. Several random deletions were performed within the proximal 7 kb of the promoter, which led to the identification of a region, whose deletion provokes a marked increase in transcriptional activity upon cytokine stimulation. Furthermore, this region is shown to repress a viral-driven luciferase construct, mainly at basal levels. An AP-1-like sequence present in this region that is specifically recognized by nuclear proteins is shown to be involved in the repressive effect. This element is capable of repressing a viral promoter, and its deletion augments cytokine-stimulated transcription. These findings are confirmed in various cell lines and suggest a general mechanism for the control of basal levels of NOSII expression, to avoid unnecessary toxicity under normal conditions.

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Citations

May 3, 2014·In Vitro Cellular & Developmental Biology. Animal·Hanbyeol LeeSe-Ran Yang
Feb 22, 2012·Cellular and Molecular Life Sciences : CMLS·Sylvie ReveneauAlena Pance
May 5, 2010·Nitric Oxide : Biology and Chemistry·Andrea PautzHartmut Kleinert
Nov 3, 2010·Scandinavian Journal of Immunology·T Qidwai, F Jamal
Feb 6, 2014·International Journal of Immunogenetics·I J T Messias-ReasonT P Velavan
Aug 18, 2005·Biochemical and Biophysical Research Communications·Valentina CoiaJürgen F J Kun
Apr 10, 2013·International Journal of Molecular Sciences·Alena Pance
Dec 13, 2003·Biological Chemistry·Hartmut KleinertUlrich Förstermann
Mar 22, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Fatima BentrariAlena Pance
Feb 14, 2004·Redox Report : Communications in Free Radical Research·Jürgen F J Kun
Oct 28, 2004·American Journal of Physiology. Renal Physiology·Zhiyuan YuBruce C Kone
Jan 13, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Galen M PieperMark B Adams
Feb 13, 2021·Brain Sciences·Arrin C Brooks, Brandon J Henderson

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