Mouse interleukin-2 receptor alpha gene expression. Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements
| Autor: | P, Sperisen, S M, Wang, E, Soldaini, M, Pla, C, Rusterholz, P, Bucher, P, Corthésy, P, Reichenbach, M, Nabholz |
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| Rok vydání: | 1995 |
| Předmět: |
Binding Sites
Base Sequence T-Lymphocytes Molecular Sequence Data NF-kappa B Receptors Interleukin-2 Thymus Gland Cell Line Mice Gene Expression Regulation Oligodeoxyribonucleotides Animals Humans Interleukin-2 RNA Messenger Promoter Regions Genetic Sequence Alignment Interleukin-1 Sequence Deletion |
| Zdroj: | The Journal of biological chemistry. 270(18) |
| ISSN: | 0021-9258 |
| Popis: | We have shown that interleukin-1 (IL-1) and IL-2 control IL-2 receptor alpha (IL-2R alpha) gene transcription in CD4-CD8- murine T lymphocyte precursors. Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma (PC60). The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic. IL-1 induces a rapid, protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation. It also primes cells to become IL-2 responsive and thereby prepares the second phase, in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts. Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness, most importantly an NF-kappa B site conserved in the human and mouse gene. IL-2 responsiveness, on the other hand, depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site. This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced. IL-2 responsiveness requires three distinct elements within the enhancer. Two of these are potential binding sites for STAT proteins. |
| Databáze: | OpenAIRE |
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