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

Chung-Yih Wang; Alexander G Bassuk; Lawrence H. Boise; Craig B Thompson; Rodrigo Bravo; Jeffrey M Leiden

doi:10.1128/mcb.14.2.1153-1159.1994

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

Chung-Yih Wang, Alexander G Bassuk, Lawrence H. Boise, Craig B Thompson, Rodrigo Bravo and Jeffrey M Leiden

Molecular and cellular biology, Vol.14(2), pp.1153-1159

02/1994

DOI: 10.1128/mcb.14.2.1153-1159.1994

PMCID: PMC358471

PMID: 8289796

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https://www.ncbi.nlm.nih.gov/pmc/articles/358471View

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Abstract

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 PB1-binding activity present in activated T-cell nuclear extracts is composed of the Elf-1, 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-cell activation.

Details

Title: Subtitle: Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors
Creators: Chung-Yih Wang - Department of Medicine, University of Chicago, Illinois 60637
Alexander G Bassuk - Department of Medicine, University of Chicago, Illinois 60637
Lawrence H. Boise - Department of Medicine, University of Chicago, Illinois 60637
Craig B Thompson - Department of Medicine, University of Chicago, Illinois 60637
Rodrigo Bravo - Department of Medicine, University of Chicago, Illinois 60637
Jeffrey M Leiden - Department of Medicine, University of Chicago, Illinois 60637
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.14(2), pp.1153-1159
DOI: 10.1128/mcb.14.2.1153-1159.1994
PMID: 8289796
PMCID: PMC358471
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Language: English
Date published: 02/1994
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020715502771

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