Mouse interleukin-2 receptor alpha gene expression. Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements.
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.
Sperisen
P
P
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Wang
S M
SM
Soldaini
E
E
Pla
M
M
Rusterholz
C
C
Bucher
P
P
Corthésy
P
P
Reichenbach
P
P
Nabholz
M
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology
D007375:Interleukin-1; D007376:Interleukin-2; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2