The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT

Esteban S. Masuda, Hiroshi Tokumitsu, Akio Tsuboi, Joseph Shlomai, Peggy Hung, Ken Ichi Arai, Naoko Arai

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in T cells is activated by the combination of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187), which mimic antigen stimulation through the T-cell receptor. We have previously shown that a fragment containing bp -95 to +27 of the mouse GM-CSF promoter can confer inducibility to reporter genes in the human Jurkat T-cell line. Here we use an in vitro transcription system to demonstrate that a cis-acting element (positions -54 to -40), referred to as CLE0, is a target for the induction signals. We observed induction with templates containing intact CLE0 but not with templates with deleted or mutated CLE0. We also observed that two distinct signals were required for the stimulation through CLE0, since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction. Stimulation probably was mediated by CLE0-binding proteins because depletion of these proteins specifically reduced GM-CSF transcription. One of the binding factors possessed biochemical and immunological features identical to those of the transcription factor AP1. Another factor resembled the T-cell-specific factor NFAT. The characteristics of these two factors are consistent with their involvement in GM-CSF induction. The presence of CLE0-like elements in the promoters of interleukin-3 (IL-3), IL-4, IL-5, GM-CSF, and NFAT sites in the IL-2 promoter suggests that the factors we detected, or related factors that recognize these sites, may account for the coordinate induction of these genes during T-cell activation.

Original languageEnglish
Pages (from-to)7399-7407
Number of pages9
JournalMolecular and Cellular Biology
Volume13
Issue number12
Publication statusPublished - Dec 1993
Externally publishedYes

Fingerprint

Granulocyte-Macrophage Colony-Stimulating Factor
T-Lymphocytes
Calcimycin
Tetradecanoylphorbol Acetate
TCF Transcription Factors
Jurkat Cells
Calcium Ionophores
Interleukin-3
Interleukin-5
Phorbol Esters
T-Cell Antigen Receptor
Cell Extracts
Reporter Genes
Interleukin-4
Genes
Interleukin-2
Carrier Proteins
Transcription Factors
Antigens
Cell Line

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT. / Masuda, Esteban S.; Tokumitsu, Hiroshi; Tsuboi, Akio; Shlomai, Joseph; Hung, Peggy; Arai, Ken Ichi; Arai, Naoko.

In: Molecular and Cellular Biology, Vol. 13, No. 12, 12.1993, p. 7399-7407.

Research output: Contribution to journalArticle

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abstract = "Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in T cells is activated by the combination of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187), which mimic antigen stimulation through the T-cell receptor. We have previously shown that a fragment containing bp -95 to +27 of the mouse GM-CSF promoter can confer inducibility to reporter genes in the human Jurkat T-cell line. Here we use an in vitro transcription system to demonstrate that a cis-acting element (positions -54 to -40), referred to as CLE0, is a target for the induction signals. We observed induction with templates containing intact CLE0 but not with templates with deleted or mutated CLE0. We also observed that two distinct signals were required for the stimulation through CLE0, since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction. Stimulation probably was mediated by CLE0-binding proteins because depletion of these proteins specifically reduced GM-CSF transcription. One of the binding factors possessed biochemical and immunological features identical to those of the transcription factor AP1. Another factor resembled the T-cell-specific factor NFAT. The characteristics of these two factors are consistent with their involvement in GM-CSF induction. The presence of CLE0-like elements in the promoters of interleukin-3 (IL-3), IL-4, IL-5, GM-CSF, and NFAT sites in the IL-2 promoter suggests that the factors we detected, or related factors that recognize these sites, may account for the coordinate induction of these genes during T-cell activation.",
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AU - Tokumitsu, Hiroshi

AU - Tsuboi, Akio

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AU - Hung, Peggy

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AU - Arai, Naoko

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