000114853 001__ 114853
000114853 005__ 20190316234107.0
000114853 037__ $$aARTICLE
000114853 245__ $$aElf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene
000114853 269__ $$a1996
000114853 260__ $$c1996
000114853 336__ $$aJournal Articles
000114853 500__ $$aErratum in: Mol Cell Biol. 1997 Apr;17(4):2351.
000114853 520__ $$aThe interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha. transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides -276 and -244, which contains NF-kappaB and SRE/CArG motifs. PRRII is a T-cell-specific enhancer, located between nucleotides -137 and -64, which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins. However, none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2. To find new regulatory regions of the IL-2R alpha gene, 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced. We identified an 86-nucleotide fragment that is 90% identical to the recently characterized murine IL-2-responsive element (mIL-2rE). This putative human IL-2rE, designated PRRIII, confers IL-2 responsiveness on a heterologous promoter. PRRIII contains a Stat protein binding site that overlaps with an EBS motif (GASd/EBSd). These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs. IL-2 induced the binding of Stat5a and b proteins to the human GASd element. To confirm the physiological relevance of these findings, we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element. Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor.
000114853 700__ $$aLecine, P.
000114853 700__ $$aAlgarte, M.
000114853 700__ $$aRameil, P.
000114853 700__ $$aBeadling, C.
000114853 700__ $$0244404$$g113607$$aBucher, P.
000114853 700__ $$aNabholz, M.
000114853 700__ $$aImbert, J.
000114853 773__ $$j16$$tMol Cell Biol$$k12$$q6829-40
000114853 8564_ $$uhttps://infoscience.epfl.ch/record/114853/files/6829.full.pdf$$zPublisher's version$$s703330$$yPublisher's version
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000114853 937__ $$aGR-BUCHER-ARTICLE-1996-006
000114853 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000114853 980__ $$aARTICLE