Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3

Douglas S. Taylor, Jacob P. Laubach, David G. Nathan, Bernard Mathey-Prevot

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Tissue-specific expression of interleukin-3 (IL-3) is mediated via cis- acting elements located within 315 base pairs of the transcription start. This is achieved in part through the positive activities of the AP-1 and Elf- 1 sites in the IL-3 promoter. The contribution to T cell-specific expression by other promoter sites was assessed in a transient expression assay with IL- 3 promoter constructs linked to a luciferase gene, focusing initially on the core binding factor (CBF) site, which is footprinted in vivo upon T cell activation. Activity of the CBF site is shown to be critically dependent on the adjacent activator site Act-1. Together the Act-1 and CBF sites form a functional unit (AC unit) with dual activity. The AC unit is demonstrated to enhance basal activity of promoters both in fibroblasts and T cells. This activity is further inducible in activated T cells, but not in fibroblasts. In addition to the already identified NIP repressor site, evidence is presented for a second repressor region that restricts promoter activity in fibroblasts. Finally, a novel positive regulatory element has been mapped in the IL-3 promoter between nucleotide -180 and -210 that leads to increased expression in T cells. Together these results demonstrate that T cell expression of IL-3 is not specified by the activity of a single tissue- specific element, but instead involves multiple interacting elements that provide both specific positive regulation in T cells and specific negative regulation in fibroblasts.

Original languageEnglish (US)
Pages (from-to)14020-14027
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number24
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Core Binding Factors
T-cells
Interleukin-3
Tissue
T-Lymphocytes
Fibroblasts
Binding Sites
Transcription Factor AP-1
Transcription
Luciferases
Genetic Promoter Regions
Base Pairing
Assays
Nucleotides
Genes
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3. / Taylor, Douglas S.; Laubach, Jacob P.; Nathan, David G.; Mathey-Prevot, Bernard.

In: Journal of Biological Chemistry, Vol. 271, No. 24, 1996, p. 14020-14027.

Research output: Contribution to journalArticle

Taylor, Douglas S. ; Laubach, Jacob P. ; Nathan, David G. ; Mathey-Prevot, Bernard. / Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 24. pp. 14020-14027.
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