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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Taylor, DS; Laubach, JP; Nathan, DG; Mathey-Prevot, B

Published Date

  • June 14, 1996

Published In

Volume / Issue

  • 271 / 24

Start / End Page

  • 14020 - 14027

PubMed ID

  • 8662845

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States