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 language | English (US) |
|---|---|
| Pages (from-to) | 14020-14027 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 271 |
| Issue number | 24 |
| DOIs | |
| State | Published - 1996 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3
AU - Taylor, Douglas S.
AU - Laubach, Jacob P.
AU - Nathan, David G.
AU - Mathey-Prevot, Bernard
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.271.24.14020
DO - 10.1074/jbc.271.24.14020
M3 - Article
C2 - 8662845
AN - SCOPUS:17544362538
VL - 271
SP - 14020
EP - 14027
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 24
ER -