Transcriptional activity of the distal CD40 ligand promoter

Francis M. Lobo*, Shuhua Xu, Celine Lee, Ramsay L. Fuleihan

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

CD40 ligand (CD40L, CD154) is a T cell cytokine with highly regulated expression that requires the transcription factor nuclear factor of activated T cells (NFAT) to bind at two sites in the proximal CD40L promoter. We have determined that the distal CD40L promoter (-500 to -1300 bp from start of transcription) conveys superior promoter activity in reporter gene assays. Within the distal promoter, we have iden tified a third NF-AT binding site, at -761 to -756. Oligonucleotides incorporating each of the three NF-AT sites cross-compete for binding of nuclear extracts from activated T cells and bind NF-ATc2 by antibody supershift. Mutation of the distal NF-AT site reduces activity of the 1300 bp CD40L promoter construct to that of the proximal 500 bp construct, which includes only two NF-AT sites. This suggests that the newly identified NF-AT site is the major mediator of transcriptional activation in the distal CD40L promoter. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)245-250
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume279
Issue number1
DOIs
StatePublished - Dec 9 2000

Fingerprint

CD40 Ligand
T-cells
NFATC Transcription Factors
T-Lymphocytes
Transcription
Reporter Genes
Oligonucleotides
Transcriptional Activation
Assays
Transcription Factors
Genes
Chemical activation
Binding Sites
Cytokines
Mutation
Antibodies

Keywords

  • CD40 ligand
  • Cytokine
  • Gene expression
  • NF-AT
  • T lymphocyte

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lobo, Francis M. ; Xu, Shuhua ; Lee, Celine ; Fuleihan, Ramsay L. / Transcriptional activity of the distal CD40 ligand promoter. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 279, No. 1. pp. 245-250.
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Transcriptional activity of the distal CD40 ligand promoter. / Lobo, Francis M.; Xu, Shuhua; Lee, Celine; Fuleihan, Ramsay L.

In: Biochemical and Biophysical Research Communications, Vol. 279, No. 1, 09.12.2000, p. 245-250.

Research output: Contribution to journalArticle

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AU - Lobo, Francis M.

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N2 - CD40 ligand (CD40L, CD154) is a T cell cytokine with highly regulated expression that requires the transcription factor nuclear factor of activated T cells (NFAT) to bind at two sites in the proximal CD40L promoter. We have determined that the distal CD40L promoter (-500 to -1300 bp from start of transcription) conveys superior promoter activity in reporter gene assays. Within the distal promoter, we have iden tified a third NF-AT binding site, at -761 to -756. Oligonucleotides incorporating each of the three NF-AT sites cross-compete for binding of nuclear extracts from activated T cells and bind NF-ATc2 by antibody supershift. Mutation of the distal NF-AT site reduces activity of the 1300 bp CD40L promoter construct to that of the proximal 500 bp construct, which includes only two NF-AT sites. This suggests that the newly identified NF-AT site is the major mediator of transcriptional activation in the distal CD40L promoter. (C) 2000 Academic Press.

AB - CD40 ligand (CD40L, CD154) is a T cell cytokine with highly regulated expression that requires the transcription factor nuclear factor of activated T cells (NFAT) to bind at two sites in the proximal CD40L promoter. We have determined that the distal CD40L promoter (-500 to -1300 bp from start of transcription) conveys superior promoter activity in reporter gene assays. Within the distal promoter, we have iden tified a third NF-AT binding site, at -761 to -756. Oligonucleotides incorporating each of the three NF-AT sites cross-compete for binding of nuclear extracts from activated T cells and bind NF-ATc2 by antibody supershift. Mutation of the distal NF-AT site reduces activity of the 1300 bp CD40L promoter construct to that of the proximal 500 bp construct, which includes only two NF-AT sites. This suggests that the newly identified NF-AT site is the major mediator of transcriptional activation in the distal CD40L promoter. (C) 2000 Academic Press.

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