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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kaminuma O,Kitamura F,Kitamura N,Miyagishi M,Taira K,Yamamoto K,Miura O,Miyatake S

doi

10.1016/j.febslet.2004.06.026

keywords:

subject

Has Abstract

pub_date

2004-07-16 00:00:00

pages

63-8

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579304007495

journal_volume

570

pub_type

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