0 5 Elf-1 Elf-1 NNP 6 9 and and CC 10 15 Stat5 Stat5 NNP 16 20 bind bind VBP 21 23 to to TO 24 25 a a DT 26 34 critical critical JJ 35 42 element element NN 43 45 in in IN 46 47 a a DT 48 51 new new JJ 52 60 enhancer enhancer NN 61 63 of of IN 64 67 the the DT 68 73 human human JJ 74 87 interleukin-2 interleukin-2 NN 88 96 receptor receptor NN 97 102 alpha alpha NN 103 107 gene gene NN 108 109 [ [ ( 109 118 published publish VBN 119 126 erratum erratum NN 127 134 appears appear VBZ 135 137 in in IN 138 141 Mol Mol NNP 142 146 Cell Cell NNP 147 151 Biol Biol NNP 152 156 1997 1997 CD 157 171 Apr;17(4):2351 apr;17(4):2351 CD 171 172 ] ] ) 174 177 The the DT 178 189 interleukin interleukin NN 190 191 2 2 CD 192 200 receptor receptor NN 201 212 alpha-chain alpha-chain NN 213 214 ( ( ( 214 219 IL-2R IL-2R NNP 220 225 alpha alpha NN 225 226 ) ) ) 227 231 gene gene NN 232 234 is be VBZ 235 236 a a DT 237 240 key key JJ 241 250 regulator regulator NN 251 253 of of IN 254 264 lymphocyte lymphocyte NN 265 278 proliferation proliferation NN 278 279 . . . 280 285 IL-2R IL-2R NNP 286 291 alpha alpha NN 292 294 is be VBZ 295 302 rapidly rapidly RB 303 306 and and CC 307 315 potently potently RB 316 323 induced induce VBN 324 326 in in IN 327 328 T t NN 329 334 cells cell NNS 335 337 in in IN 338 346 response response NN 347 349 to to TO 350 359 mitogenic mitogenic JJ 360 367 stimuli stimulus NNS 367 368 . . . 369 380 Interleukin Interleukin NNP 381 382 2 2 CD 383 384 ( ( ( 384 388 IL-2 il-2 NN 388 389 ) ) ) 390 400 stimulates stimulate VBZ 401 406 IL-2R il-2r NN 407 412 alpha alpha NN 413 426 transcription transcription NN 426 427 , , , 428 435 thereby thereby RB 436 446 amplifying amplify VBG 447 457 expression expression NN 458 460 of of IN 461 464 its its PRP$ 465 468 own own JJ 469 482 high-affinity high-affinity JJ 483 491 receptor receptor NN 491 492 . . . 493 498 IL-2R IL-2R NNP 499 504 alpha alpha NN 505 518 transcription transcription NN 519 521 is be VBZ 522 524 at at IN 525 530 least least JJS 531 533 in in IN 534 538 part part NN 539 549 controlled control VBN 550 552 by by IN 553 556 two two CD 557 565 positive positive JJ 566 576 regulatory regulatory JJ 577 584 regions region NNS 584 585 , , , 586 590 PRRI PRRI NNP 591 594 and and CC 595 600 PRRII PRRII NNP 600 601 . . . 602 606 PRRI PRRI NNP 607 609 is be VBZ 610 612 an an DT 613 622 inducible inducible JJ 623 631 proximal proximal JJ 632 640 enhancer enhancer NN 640 641 , , , 642 649 located located JJ 650 657 between between IN 658 669 nucleotides nucleotide NNS 670 674 -276 -276 CD 675 678 and and CC 679 683 -244 -244 CD 683 684 , , , 685 690 which which WDT 691 699 contains contain VBZ 700 709 NF-kappaB NF-kappaB NNP 710 713 and and CC 714 722 SRE/CArG SRE/CArG NNP 723 729 motifs motif NNS 729 730 . . . 731 736 PRRII PRRII NNP 737 739 is be VBZ 740 741 a a DT 742 757 T-cell-specific t-cell-specific JJ 758 766 enhancer enhancer NN 766 767 , , , 768 775 located located JJ 776 783 between between IN 784 795 nucleotides nucleotide NNS 796 800 -137 -137 CD 801 804 and and CC 805 808 -64 -64 CD 808 809 , , , 810 815 which which WDT 816 821 binds bind VBZ 822 825 the the DT 826 841 T-cell-specific t-cell-specific JJ 842 845 Ets Ets NNP 846 853 protein protein NN 854 859 Elf-1 elf-1 NN 860 863 and and CC 864 872 HMG-I(Y) hmg-i(y) NN 873 881 proteins protein NNS 881 882 . . . 883 890 However however RB 890 891 , , , 892 896 none none NN 897 899 of of IN 900 905 these these DT 906 914 proximal proximal JJ 915 922 regions region NNS 923 930 account account VBP 931 934 for for IN 935 938 the the DT 939 948 induction induction NN 949 951 of of IN 952 957 IL-2R IL-2R NNP 958 963 alpha alpha NN 964 977 transcription transcription NN 978 980 by by IN 981 985 IL-2 il-2 NN 985 986 . . . 987 989 To to TO 990 994 find find VB 995 998 new new JJ 999 1009 regulatory regulatory JJ 1010 1017 regions region NNS 1018 1020 of of IN 1021 1024 the the DT 1025 1030 IL-2R IL-2R NNP 1031 1036 alpha alpha NN 1037 1041 gene gene NN 1041 1042 , , , 1043 1046 8.5 8.5 CD 1047 1049 kb kb NN 1050 1052 of of IN 1053 1056 the the DT 1057 1058 5 5 CD 1058 1059 ’ ' SYM 1060 1063 end end NN 1064 1073 noncoding noncoding JJ 1074 1082 sequence sequence NN 1083 1085 of of IN 1086 1089 the the DT 1090 1095 IL-2R IL-2R NNP 1096 1101 alpha alpha NN 1102 1106 gene gene NN 1107 1111 have have VBP 1112 1116 been be VBN 1117 1126 sequenced sequence VBN 1126 1127 . . . 1128 1130 We we PRP 1131 1141 identified identify VBD 1142 1144 an an DT 1145 1158 86-nucleotide 86-nucleotide JJ 1159 1167 fragment fragment NN 1168 1172 that that WDT 1173 1175 is be VBZ 1176 1178 90 90 CD 1178 1179 % % NN 1180 1189 identical identical JJ 1190 1192 to to TO 1193 1196 the the DT 1197 1205 recently recently RB 1206 1219 characterized characterize VBN 1220 1226 murine murine JJ 1227 1242 IL-2-responsive il-2-responsive JJ 1243 1250 element element NN 1251 1252 ( ( ( 1252 1259 mIL-2rE mil-2re NN 1259 1260 ) ) ) 1260 1261 . . . 1262 1266 This this DT 1267 1275 putative putative JJ 1276 1281 human human JJ 1282 1288 IL-2rE il-2re NN 1288 1289 , , , 1290 1300 designated designate VBN 1301 1307 PRRIII PRRIII NNP 1307 1308 , , , 1309 1316 confers confer VBZ 1317 1321 IL-2 il-2 NN 1322 1336 responsiveness responsiveness NN 1337 1339 on on IN 1340 1341 a a DT 1342 1354 heterologous heterologous JJ 1355 1363 promoter promoter NN 1363 1364 . . . 1365 1371 PRRIII PRRIII NNP 1372 1380 contains contain VBZ 1381 1382 a a DT 1383 1387 Stat Stat NNP 1388 1395 protein protein NN 1396 1403 binding binding NN 1404 1408 site site NN 1409 1413 that that WDT 1414 1422 overlaps overlap VBZ 1423 1427 with with IN 1428 1430 an an DT 1431 1434 EBS EBS NNP 1435 1440 motif motif NN 1441 1442 ( ( ( 1442 1451 GASd/EBSd GASd/EBSd NNP 1451 1452 ) ) ) 1452 1453 . . . 1454 1459 These these DT 1460 1463 are be VBP 1464 1473 essential essential JJ 1474 1477 for for IN 1478 1482 IL-2 il-2 NN 1483 1495 inducibility inducibility NN 1496 1498 of of IN 1499 1509 PRRIII/CAT PRRIII/CAT NNP 1510 1518 reporter reporter NN 1519 1529 constructs construct NNS 1529 1530 . . . 1531 1535 IL-2 il-2 NN 1536 1543 induced induce VBD 1544 1547 the the DT 1548 1555 binding binding NN 1556 1558 of of IN 1559 1565 Stat5a Stat5a NNP 1566 1569 and and CC 1570 1571 b b NN 1572 1580 proteins protein NNS 1581 1583 to to TO 1584 1587 the the DT 1588 1593 human human JJ 1594 1598 GASd gasd NN 1599 1606 element element NN 1606 1607 . . . 1608 1610 To to TO 1611 1618 confirm confirm VB 1619 1622 the the DT 1623 1636 physiological physiological JJ 1637 1646 relevance relevance NN 1647 1649 of of IN 1650 1655 these these DT 1656 1664 findings finding NNS 1664 1665 , , , 1666 1668 we we PRP 1669 1676 carried carry VBD 1677 1680 out out RP 1681 1683 in in FW 1684 1688 vivo vivo FW 1689 1701 footprinting footprinting NN 1702 1713 experiments experiment NNS 1714 1719 which which WDT 1720 1726 showed show VBD 1727 1731 that that IN 1732 1743 stimulation stimulation NN 1744 1746 of of IN 1747 1752 IL-2R IL-2R NNP 1753 1758 alpha alpha NN 1759 1769 expression expression NN 1770 1780 correlated correlate VBD 1781 1785 with with IN 1786 1795 occupancy occupancy NN 1796 1798 of of IN 1799 1802 the the DT 1803 1807 GASd gasd NN 1808 1815 element element NN 1815 1816 . . . 1817 1820 Our our PRP$ 1821 1825 data datum NNS 1826 1837 demonstrate demonstrate VBP 1838 1839 a a DT 1840 1845 major major JJ 1846 1850 role role NN 1851 1853 of of IN 1854 1857 the the DT 1858 1867 GASd/EBSd gasd/ebsd NN 1868 1875 element element NN 1876 1878 in in IN 1879 1884 IL-2R IL-2R NNP 1885 1890 alpha alpha NN 1891 1901 regulation regulation NN 1902 1905 and and CC 1906 1913 suggest suggest VBP 1914 1918 that that IN 1919 1922 the the DT 1923 1938 T-cell-specific t-cell-specific JJ 1939 1944 Elf-1 elf-1 NN 1945 1951 factor factor NN 1952 1955 can can MD 1956 1961 serve serve VB 1962 1964 as as IN 1965 1966 a a DT 1967 1982 transcriptional transcriptional JJ 1983 1992 repressor repressor NN 1992 1993 . . .