ROG, Repressor of GATA, Regulates the Expression of Cytokine Genes

Miaw, Shi‐Chuen; Choi, Andrew; Yu, En-Ping; Kishikawa, Hiroko; Ho, I‐Cheng

doi:10.1016/s1074-7613(00)80185-5

Cited by 130 publications

(131 citation statements)

References 50 publications

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“…S2). We did not find evidence for differential modulation of GATA3 activity in CD4 and CD8 SP cells by co-factors, because RT-PCR analyses of CD2-GATA3 transgenic CD4-Cre Gata3 f/f CD4 and CD8 SP cell fractions did not reveal differences in the expression of the GATA3 cofactors friend of GATA (FOG) or repressor of GATA (ROG) [27,28] (data not shown).…”

Section: Enforced Gata3 Expression Does Not Affect Cd4/ Cd8 Lineage Cmentioning

confidence: 86%

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

et al. 2007

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The transcription factor GATA3 is essential at multiple stages of T cell development, including the earliest double-negative stages, b-selection and CD4 single-positive thymocytes. Here, we show that in CD2-GATA3 transgenic mice, with enforced GATA3 expression driven by the CD2 promoter, thymocytes have reduced levels of CD5, which is a negative regulator of TCR signaling participating in TCR repertoire fine-tuning. Reduction of CD5 expression was most prominent in CD4 + CD8 + double-positive (DP) cells and was associated with increased levels of the transcription factor E2A. Conversely, GATA3-deficient DP thymocytes showed consistently higher CD5 levels and defective TCR up-regulation during their development towards the CD4 lo CD8 lo subpopulation. CD2-GATA3 transgenic mice carrying the MHC class II-restricted TCR DO11.10 also manifested decreased CD5 levels. As in these TCR-transgenic mice reduced CD5 expression cannot result from an effect of GATA3 on repertoire selection, we conclude that enforced GATA3 interferes with the developmentally regulated increase of CD5 levels. Enforced GATA3 expression in DO11.10 transgenic mice was also accompanied by enhanced TCR expression during CD4 positive selection. Because GATA3 is induced by TCR signaling in DP thymocytes, our findings indicate that GATA3 establishes a positive feedback loop that increases TCR surface expression in developing CD4 lineage cells.

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Section: Enforced Gata3 Expression Does Not Affect Cd4/ Cd8 Lineage Cmentioning

confidence: 86%

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

et al. 2007

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“…3,31,32 A better understanding of the cis-and trans-acting factors that participate in CD154 expression should assist in identifying those factors involved in CD154 dysregulation in autoimmune states. 14 or a dominant-negative version of GATA-3 (KRR mutant; full bars). 15 Results are representative of one of four experiments performed.…”

Section: Discussionmentioning

confidence: 99%

“…The ROG expression plasmid has been previously described. 14 For reporter gene assays, primary human CD4 T cells were transiently cotransfected with luciferase reporter plasmids (see above) along with an expression vector (or control plasmid) using our own published protocol. 42 Cells were stimulated in duplicate samples with phorbol 13-myristate 12-acetate (PMA) and ionomycin for 6 h and cell lysates were analyzed for firefly luciferase activity by luminometry as described.…”

Section: Methodsmentioning

confidence: 99%

A T-cell-specific CD154 transcriptional enhancer located just upstream of the promoter

Brunner

Genin

et al. 2008

Genes Immun

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CD154 (CD40-ligand) is a critical immune regulator. CD154 expression is tightly regulated and largely restricted to activated CD4 T cells. Using DNase I hypersensitivity site (HSS) mapping, we identified two novel HSS mapping to the human CD154 promoter element and just upstream. Both HSS were activation independent and CD4 T-cell specific. Approximately 350 bp of DNA sequence flanking the upstream HSS site was highly conserved between mouse and man, and was rich in binding sites for GATA and NFAT proteins. Gel shift and chromatin immunoprecipitation assays demonstrated both NFAT1 and the Th2 factor, GATA-3, bound this enhancer element in vitro and in vivo, respectively. A PstI/XbaI 345 bp fragment of this region acted as a transcriptional enhancer of the CD154 promoter in primary human CD4 T cells. Overexpression of repressor of GATA and a dominant negative GATA-3 protein independently inhibited transcription, whereas overexpression of wild-type GATA-3 enhanced transcriptional activity, by this element in primary CD4 T cells. Moreover, more interleukin-4-producing CD4 T cells expressed CD154 following activation than interferon-g-producing CD4 T cells. Thus, we identified a novel T-cell-specific, GATA-3 responsive, CD154 transcriptional enhancer, which may contribute to increased propensity of Th2 cells to express CD154.

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“…5). ROG was originally reported to be a repressor of GATA3-induced transactivation of the IL-4 and IL-5 promoters in the M12 B and EL-4 T cell lines by preventing GATA3 from binding to DNA (37). GATA3 is required for chromatin remodeling of the IL-4 and IL-13 gene loci (24) and the IL-5 gene locus (38).…”

Section: Discussionmentioning

confidence: 99%

STAT6-Dependent Differentiation and Production of IL-5 and IL-13 in Murine NK2 Cells

Katsumoto

Kimura

Yamashita

et al. 2004

The Journal of Immunology

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NK cells differentiate into either NK1 or NK2 cells that produce IFN-γ or IL-5 and IL-13, respectively. Little is known, however, about the molecular mechanisms that control NK1 and NK2 cell differentiation. To address these questions, we established an in vitro mouse NK1/NK2 cell differentiation culture system. For NK1/NK2 cell differentiation, initial stimulation with PMA and ionomycin was required. The in vitro differentiated NK2 cells produced IL-5 and IL-13, but the levels were 20 times lower than those of Th2 or T cytotoxic (Tc)2 cells. No detectable IL-4 was produced. Freshly prepared NK cells express IL-2Rβ, IL-2RγC, and IL-4Rα. After stimulation with PMA and ionomycin, NK cells expressed IL-2Rα. NK1 cells displayed higher cytotoxic activity against Yac-1 target cells. The levels of GATA3 protein in developing NK2 cells were approximately one-sixth of those in Th2 cells. Both NK1 and NK2 cells expressed large amounts of repressor of GATA, the levels of which were equivalent to CD8 Tc1 and Tc2 cells and significantly higher than those in Th2 cells. The levels of histone hyperacetylation of the IL-4 and IL-13 gene loci in NK2 cells were very low and equivalent to those in naive CD4 T cells. The production of IL-5 and IL-13 in NK2 cells was found to be STAT6 dependent. Thus, similar to Th2 cells, NK2 cell development is dependent on STAT6, and the low level expression of GATA3 and the high level expression of repressor of GATA may influence the unique type 2 cytokine production profiles of NK2 cells.

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ROG, Repressor of GATA, Regulates the Expression of Cytokine Genes

Cited by 130 publications

References 50 publications

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

A T-cell-specific CD154 transcriptional enhancer located just upstream of the promoter

STAT6-Dependent Differentiation and Production of IL-5 and IL-13 in Murine NK2 Cells

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