Novel CD28-Responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor α-Chain Locus

Yeh, Jung-Hua; Lécine, Patrick; Nunès, Jacques A.; Spicuglia, Salvatore; Ferrier, Pierre; Olive, Daniel; Imbert, Jean

doi:10.1128/mcb.21.14.4515-4527.2001

Cited by 31 publications

(29 citation statements)

References 69 publications

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“…PRRI is presumably a T cell receptor response element as it contains an NF-B binding site that is required for IL-2R␣ promotor activity in response to PHA or PMA (15), whereas PRRIII and PRRIV (37)(38)(39)(40) are both required for IL-2-induced IL-2R␣ induction. A fifth element is a CD28 response element (41). Thus, in the IL-2R␣ gene, different enhancer-like elements differentially respond to different stimuli.…”

Section: Discussionmentioning

confidence: 99%

“…One of these genes, the IL-2R␣ gene is regulated by at least five positive regulatory regions (PRRs) (15,(37)(38)(39)(40)(41). PRRI is presumably a T cell receptor response element as it contains an NF-B binding site that is required for IL-2R␣ promotor activity in response to PHA or PMA (15), whereas PRRIII and PRRIV (37)(38)(39)(40) are both required for IL-2-induced IL-2R␣ induction.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of γc-Family Cytokine Target Genes

Kovanen¹,

Rosenwald²,

Fu³

et al. 2003

Journal of Biological Chemistry

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Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 form a family of cytokines based on their sharing the common cytokine receptor ␥ chain, ␥ c , which is mutated in X-linked severe combined immunodeficiency (SCID). As a step toward further elucidating the mechanism of action of these cytokines in T-cell biology, we compared the gene expression profiles of IL-2, IL-4, IL-7, and IL-15 in T cells using cDNA microarrays. IL-2, IL-7, and IL-15 each induced a highly similar set of genes, whereas IL-4 induced distinct genes correlating with differential STAT protein activation by this cytokine. One gene induced by IL-2, IL-7, and IL-15 but not IL-4 was dualspecificity phosphatase 5 (DUSP5). In IL-2-dependent CTLL-2 cells, we show that IL-2-induced ERK-1/2 activity was inhibited by wild type DUSP5 but markedly increased by an inactive form of DUSP5, suggesting a negative feedback role for DUSP5 in IL-2 signaling. Our findings provide insights into the shared versus distinctive actions by different members of the ␥ c family of cytokines. Moreover, we have identified a DUSP5-dependent negative regulatory pathway for MAPK activity in T cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Analysis of γc-Family Cytokine Target Genes

Kovanen¹,

Rosenwald²,

Fu³

et al. 2003

Journal of Biological Chemistry

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“…In the mouse gene, an additional regulatory element at Ϫ576 to Ϫ667 that contains binding sites for NFAT and AP-1 proteins is also required for T cell receptor-mediated induction of IL-2R␣ chain expression (27). Recently, two additional elements in the human gene have been identified, a CD28 responsive element (CD28rE) at Ϫ8.5 kB that binds CREB/ATF/AP-1 family members (28) and an intron 1 enhancer at ϩ3389 to ϩ3596 (homologous to ϩ2539 to ϩ2740 in the mouse gene) that binds STAT5 and AP-1 proteins (29,30). Intermolecular interactions between the complexes bound to PRRI and PRRII, and presumably factors binding to other elements as well, result in a highly ordered stereospecific complex thought to be crucial to regulated CD25 transcription (21).…”

Section: Interleukin-12 (Il-12)mentioning

confidence: 99%

STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus

O'Sullivan

Chang²,

et al. 2004

Journal of Biological Chemistry

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Interleukin 1 is a pleiotropic cytokine produced from macrophages and dendritic cells, which induces several responses in T cells including increased proliferation, increased cytotoxic activity, and Th1 differentiation (1). IL-12 activates several signaling pathways that may mediate these biological activities including p38 MAPK and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway (2-5). Upon binding of IL-12, both chains of the IL-12 receptor (IL-12R␤1 and IL-12R␤2) heterodimerize and activate the associated JAKs, TYK2, and JAK2. The IL-12R␤2 chain is subsequently tyrosine phosphorylated and recruits STAT4 to a specific docking site where it is itself phosphorylated (6). The phosphorylated STAT4 monomers then homodimerize and translocate into the nucleus. STAT4 is required for many of the functions of IL-12 including the induction of IFN-␥ and the differentiation of Th1 cells (7,8).Once in the nucleus, STAT4 binds to a cognate binding sequence within IL-12 responsive genes to subsequently mediate activation of transcription (9 -11). Several IL-12 responsive genes that require STAT4 for transcriptional activation have been identified including IFN-␥ (7-9, 12), IL-18R␣ (13, 14), ERM (15) and IRF-1 (10, 11). STAT4 may interact with other transcription factors at a promoter through several domains, including the C-terminal "transactivation domain." However, both STAT4 isoforms, STAT4␣ and STAT4␤ (16), the latter of which lacks the C-terminal 40 amino acids encompassing the putative transcription activation domain, are able to activate transcription and mediate many IL-12 responses. This suggests that interactions of other transcription factors with the STAT4 transactivation domain are not required for all STAT4-dependent responses. Furthermore, the events that STAT4 initiates at a promoter, and the kinetics with which they occur have not been characterized.CD25 is the ␣ chain of the high affinity IL-2 receptor complex. CD25 is only expressed upon T cell activation, and expression is further modulated by IL-2 stimulation. Transcription of CD25 is regulated by multiple transcription factors that bind to elements termed positive regulatory regions (PRR) in the CD25 promoter and intronic regions. PRRI is located around 260 nucleotides upstream of the major transcription initiation sites in the mouse gene (Ϫ276 to Ϫ244 in human) (17-19) and binds NF-B and serum response factor (20). PR-RII is around Ϫ100 in the mouse gene (Ϫ137 to Ϫ64 in human) and binds . PRRIII, also known as the IL-2 responsive element (IL-2rE), is located Ϫ1306 to Ϫ1387 in the mouse gene (Ϫ3780 to Ϫ3703 in human), and one of the tandem STAT5 binding sites overlaps a binding site for . In the mouse gene, an additional regulatory element at Ϫ576 to Ϫ667 that contains binding sites for NFAT and AP-1 proteins is also required for T cell receptor-mediated induction of IL-2R␣ chain expression (27). Recently, two additional elements in the human gene have been identified, a CD28 responsive element (CD28rE) at Ϫ8.5 kB t...

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“…After cross-linking and sonication, the chromatin extract was immunoprecipitated by a commercial, GATA4-specific mouse monoclonal antibody and the corresponding DNA fragments were purified as described previously (35). Portions of the seven characterized conserved regions containing putative GATA binding sites plus GATA-less CR3 were amplified by PCR using specific primer pairs (Table 1) and quantified using SYBR Green chemistry and a Light Cycler 2 (Roche Diagnostics).…”

Section: Gata4 Is Bound In Vivo To Several Locations In the Erbb2 Genmentioning

confidence: 99%

A Negative Feedback Regulatory Loop Associates the Tyrosine Kinase Receptor ERBB2 and the Transcription Factor GATA4 in Breast Cancer Cells

Hua

Zhu

Rosa

et al. 2009

Molecular Cancer Research

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Overexpression of the ERBB2 gene, linked to genomic and transcriptional amplifications, is a poor prognosis indicator in 25% to 30% of breast cancers. In contrast to some well-documented genomic amplifications, molecular mechanisms leading to ERBB2 transcriptional overexpression remain poorly characterized. Gene expression analyses of breast cancer have characterized distinct transcriptional signatures allowing a molecular classification of breast carcinoma. Coexpression of the ERBB2 and GATA4 genes was originally observed in tumors. Both genes are essential for cardiovascular development and GATA4 has been proposed to control the transcription of critical genes for the differentiation and the function of myocardium. We determined that ERBB2-targeted small interfering RNA repressed both ERBB2 and GATA4 genes, whereas GATA4-targeted small interfering RNA repressed GATA4 and activated ERBB2 transcription. Transfected GATA4-expressing construct repressed ERBB2 promoter. Phylogenetic foot printing revealed multiple putative GATA4 binding sites conserved in mammals within the ERBB2 promoter region. Chromatin immunoprecipitation showed that GATA4 binds specifically to several ERBB2 gene noncoding regions. Electrophoretic mobility shift assay revealed GATA4 binding to a well-conserved consensus motif. Site-directed mutagenesis confirmed the role of this new regulatory element for the activity of the ERBB2 gene enhancer. In agreement with a repressor role of GATA4 on ERBB2 gene expression balanced by ERBB2 activation of the GATA4 gene, a negative correlation between the relative levels of ERBB2 and GATA4 mRNA was observed in breast cancer cell lines and breast tumor samples. We propose that the negative feedback loop linking ERBB2 and GATA4 plays a role in the transcriptional dysregulation of ERBB2 gene expression in breast cancer. (Mol Cancer Res 2009;7(3):402 -14)

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Novel CD28-Responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor α-Chain Locus

Cited by 31 publications

References 69 publications

Analysis of γc-Family Cytokine Target Genes

Analysis of γc-Family Cytokine Target Genes

STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus

A Negative Feedback Regulatory Loop Associates the Tyrosine Kinase Receptor ERBB2 and the Transcription Factor GATA4 in Breast Cancer Cells

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