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

Osamu Kaminuma; Fujiko Kitamura; Noriko Kitamura; Makoto Miyagishi; Kazunari Taira; Koh Yamamoto; Osamu Miura; Shoichiro Miyatake

doi:10.1016/j.febslet.2004.06.026

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

FEBS Lett. 2004 Jul 16;570(1-3):63-8. doi: 10.1016/j.febslet.2004.06.026.

Authors

Osamu Kaminuma¹, Fujiko Kitamura, Noriko Kitamura, Makoto Miyagishi, Kazunari Taira, Koh Yamamoto, Osamu Miura, Shoichiro Miyatake

Affiliation

¹ Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.

PMID: 15251440
DOI: 10.1016/j.febslet.2004.06.026

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Binding Sites
Cell Nucleus / metabolism
DNA, Complementary / metabolism
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / physiology*
Down-Regulation
Enhancer Elements, Genetic*
Flow Cytometry
GATA3 Transcription Factor
Gene Expression Regulation
Genes, Reporter
Genetic Vectors
Green Fluorescent Proteins
Humans
Immunoblotting
Interferon-gamma / genetics*
Interleukin-4 / metabolism
Jurkat Cells
Luminescent Proteins / metabolism
Models, Genetic
Molecular Sequence Data
Plasmids / metabolism
Promoter Regions, Genetic*
Protein Binding
RNA Interference
RNA, Messenger / metabolism
STAT4 Transcription Factor
Th1 Cells / metabolism
Th2 Cells / metabolism
Time Factors
Trans-Activators / metabolism
Trans-Activators / physiology*

Substances

DNA, Complementary
DNA-Binding Proteins
GATA3 Transcription Factor
GATA3 protein, human
Luminescent Proteins
RNA, Messenger
STAT4 Transcription Factor
STAT4 protein, human
Trans-Activators
Green Fluorescent Proteins
Interleukin-4
Interferon-gamma