The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity.

Nimer, S.; Fraser, John K.; Richards, Jo Anne S.; Lynch, Maureen; Gasson, Judith C.

doi:10.1128/mcb.10.11.6084

Cited by 47 publications

(35 citation statements)

References 18 publications

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“…An inducible NFAT-like complex (Masuda et al, 1993) also displays weak binding to CLE0. The CLE0 region has been described as a part of a triple repeat CATT(A/T) element by others (Nimer et al, 1990). In addition, other factors have recently been shown to be involved in GM ± CSF transcriptional control.…”

Section: Introductionmentioning

confidence: 99%

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

et al. 1997

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Activation of helper T cells results in coordinate expression of a number of cytokines involved in di erentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony stimulating factor (GM ± CSF) is one such cytokine, whose increased expression results mostly from increases in transcription. Cis-acting elements with NFkB, AP1 and ETS-like binding motifs have been identi®ed in the promoter region of the GM ± CSF gene, and are important or essential for transcriptional activity following T cell activation. ETS1 is a transcription factor of the ETS family that is expressed in T cells. We have previously shown that ETS1 can transactivate GM ± CSF in Jurkat T cells, but only after the cells have been stimulated by treatment with PMA and ionomycin, agents that mimic T cell activation. Thus we proposed that ETS1, which is expressed constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible factors. Here we show that ETS1 can transactivate a GM ± CSF reporter construct in unstimulated Jurkat cells, providing that either NFkB or AP1 transcription factors are supplied by co-transfection. We con®rm that binding of endogenous NFkB and AP1 is induced following PMA/ionomycin treatment of T cells. Transactivation by ETS1, NFkB and AP1 is synergistic, and mutation of the individual binding sites reveals that the transcriptional activities of these factors are interdependent. Our results suggest that constitutive ETS1, and inducible NFkB and AP1, cooperate as part of a higher order transcriptional complex in activated T cells.

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Section: Introductionmentioning

confidence: 99%

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

et al. 1997

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“…A CATT repeated element also exists in the promoter of human granulocyte-macrophage colony-stimulating factor (GM-CSF), and is required for promoter activity. 32,33 It has been shown that the nuclear factor YY1, 34 and more recently the factors AP-1 and SP-1, can from complexes with this region of the GM-CSF promoter. 35 Whether any of these same factors also influence the activity of the MIF CATT repeat remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis

et al. 2002

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“…Subsequent in vitro mutagenesis experiments demonstrated that this region is required for the inducible expression of the intact GM-CSF promoter in T cells. Interestingly, the PB1 sequence motif is highly conserved in both the murine and human GM-CSF genes (24) and is also present in the 5' flanking regions of the human and murine IL-5 genes (29).Although these previous studies demonstrated that the PB1 element is required for inducible expression of the GM-CSF gene in T cells, it remained unclear whether this element alone was sufficient to confer inducible expression on a minimal promoter in T cells. More importantly, the identities of the transcription factors that bind to PB1 to mediate GM-CSF transcriptional activation remained un-clear.…”

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confidence: 88%

Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors.

Wang¹,

Bassuk²,

Boise³

et al. 1994

Mol. Cell. Biol.

124

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The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation. The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor. A highly conserved 19-bp element located immediately 5' of the human GM-CSF TATA box (bp -34 to -52), herein called purine box 1 (PB1), has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation. The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes. In this report, we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells. In addition, we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation. Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors. In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells. Using antibodies specific for different Ets and AP-1 family members, we demonstrate that the major inducible PBI-binding activity present in activated T-cell nuclear extracts is composed of the Elf-i, c-Fos, and JunB transcription factors. Taken together, these results suggest that cooperative interactions between specific Ets and AP-1 family members are important in regulating inducible gene expression following T-celi activation.The activation of normal peripheral blood T cells results in the precisely orchestrated transcriptional induction of more than 100 new genes, many of which are important mediators of the inflammatory response to foreign pathogens (7). Activation-specific T-cell genes include those encoding cell surface molecules that induce important changes in T-cell adhesion as well as a number of lymphokines, such as IL-2 (interleukin-2), IL-3, gamma interferon, and GM-CSF (granulocyte-macrophage colony-stimulating factor), which can function in both autocrine and paracrine pathways to control the proliferation and function of multiple inflammatory cell types (7). Given the importance of inducible T-cell genes in modulating the inflammatory response, the elucidation of the molecular mechanisms underlying inducible transcription in T cells may yield important insights into both normal and pathophysiological T-cell function.Several genes have been characterized extensively as model systems for understanding inducible transcription in T cells. These include the IL-2 (2, 4, 8, 10), 30), 6,24), and human immunodeficiency virus long terminal repeat (1,18,20,22) genes. The GM-CSF gene is among the best charac...

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The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity.

Cited by 47 publications

References 18 publications

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis

Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors.

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