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A stimulation-dependent alternate core promoter links lymphotoxin α expression with TGF-β1 and fibroblast growth factor-7 signaling in primary human T cells.

Authors :
Yokley BH
Selby ST
Posch PE
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 May 01; Vol. 190 (9), pp. 4573-84. Date of Electronic Publication: 2013 Apr 01.
Publication Year :
2013

Abstract

Lymphotoxin (LT)-α regulates many biologic activities, yet little is known of the regulation of its gene. In this study, the contribution to LTA transcriptional regulation of the region between the transcription and translation start sites (downstream segment) was investigated. The LTA downstream segment was found to be required for, and alone to be sufficient for, maximal transcriptional activity in both T and B lymphocytes. The latter observation suggested that an alternate core promoter might be present in the downstream segment. Characterization of LTA mRNAs isolated from primary and from transformed human T cells under different stimulation conditions identified eight unique transcript variants (TVs), including one (LTA TV8) that initiated within a polypyrimidine tract near the 3' end of the downstream segment. Further investigation determined that the LTA downstream segment alternate core promoter that produces the LTA TV8 transcript most likely consists of a stimulating protein 1 binding site and an initiator element and that factors involved in transcription initiation (stimulating protein 1, TFII-I, and RNA polymerase II) bind to this LTA region in vivo. Interestingly, the LTA downstream segment alternate core promoter was active only after specific cellular stimulation and was the major promoter used when human T cells were stimulated with TGF-β1 and fibroblast growth factor-7. Most importantly, this study provides evidence of a direct link for crosstalk between T cells and epithelial/stromal cells that has implications for LT signaling by T cells in the cooperative regulation of various processes typically associated with TGF-βR and fibroblast growth factor-R2 signaling.

Details

Language :
English
ISSN :
1550-6606
Volume :
190
Issue :
9
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
23547113
Full Text :
https://doi.org/10.4049/jimmunol.1201068