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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.
- 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.
- Subjects :
- B-Lymphocytes immunology
B-Lymphocytes metabolism
Base Sequence
Binding Sites genetics
Binding Sites immunology
Cell Line, Tumor
DNA-Binding Proteins genetics
DNA-Binding Proteins immunology
DNA-Binding Proteins metabolism
Epithelial Cells immunology
Epithelial Cells metabolism
Fibroblast Growth Factor 7 immunology
Fibroblast Growth Factor 7 metabolism
Gene Expression Regulation immunology
Humans
Jurkat Cells
Lymphotoxin-alpha genetics
Lymphotoxin-alpha immunology
Molecular Sequence Data
Polypyrimidine Tract-Binding Protein genetics
Polypyrimidine Tract-Binding Protein immunology
Polypyrimidine Tract-Binding Protein metabolism
Promoter Regions, Genetic
RNA Polymerase II genetics
RNA Polymerase II immunology
RNA Polymerase II metabolism
RNA, Messenger genetics
RNA, Messenger immunology
Signal Transduction immunology
Sp1 Transcription Factor genetics
Sp1 Transcription Factor immunology
Sp1 Transcription Factor metabolism
Stromal Cells immunology
Stromal Cells metabolism
T-Lymphocytes immunology
Transcription Factors, TFII genetics
Transcription Factors, TFII immunology
Transcription Factors, TFII metabolism
Transcription, Genetic immunology
Transcriptional Activation immunology
Transforming Growth Factor beta1 genetics
Transforming Growth Factor beta1 immunology
Fibroblast Growth Factor 7 genetics
Lymphotoxin-alpha biosynthesis
T-Lymphocytes metabolism
Transforming Growth Factor beta1 metabolism
Subjects
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