GATA-3 suppresses IFN-gamma promoter activity independently of binding to cis-regulatory elements

FEBS Letters
Osamu KaminumaShoichiro Miyatake

Abstract

The regulatory mechanism by which GATA-3 suppresses IFN-gamma gene expression was investigated. A reduction of GATA-3 using RNA interference technology enhanced, whereas overexpression of GATA-3 suppressed IFN-gamma mRNA expression. IL-4 expression was reciprocally affected by GATA-3. GATA-3-mediated down-regulation of IFN-gamma was achieved through the inhibition of its promoter/enhancer activity. Two GATA elements located in the cis-regulatory elements did not contribute to the suppression of IFN-gamma promoter activity, even though they behaved as binding sites for GATA-3. The effect of GATA-3 on IFN-gamma promoter was lost upon removal of the region encompassing -257 to -172. Among several transcription factors putatively interacting with this region, Stat4, which enhanced IFN-gamma promoter activity, was down-regulated by GATA-3 at gene transcription level. Although GATA-3 has the capacity to interact with the cis-regulatory elements, it suppresses IFN-gamma gene transcription via down-regulation of Stat4.

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Citations

Nov 20, 2009·The Journal of Biological Chemistry·Rajan M ThomasAndrew D Wells
Aug 15, 2008·The Journal of Biological Chemistry·Ryo ShinnakasuToshinori Nakayama
Mar 17, 2010·Infection and Immunity·Norihiro HaraguchiNobuyuki Hizawa
Jun 11, 2005·International Archives of Allergy and Immunology·Osamu KaminumaShoichiro Miyatake
Aug 9, 2007·International Archives of Allergy and Immunology·Noriko KitamuraAkio Mori
Jun 25, 2008·International Archives of Allergy and Immunology·Kazuya SuzukiAkio Mori
Apr 4, 2014·Veterinary Immunology and Immunopathology·Anne-Marie ChausséPhilippe Velge
May 20, 2008·Annals of Medicine·Kirsi J RautajokiRiitta Lahesmaa
Mar 12, 2009·Biochemical and Biophysical Research Communications·Noriko KitamuraOsamu Kaminuma
Jul 4, 2006·The American Journal of Pathology·Toru KimuraKiyohisa Sekizawa
Nov 29, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Osamu KaminumaTakachika Hiroi
Dec 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Osamu KaminumaShoichiro Miyatake

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