0 8 Positive positive JJ 9 12 and and CC 13 21 negative negative JJ 22 32 regulation regulation NN 33 35 of of IN 36 40 IL-2 il-2 NN 41 45 gene gene NN 46 56 expression expression NN 56 57 : : : 58 62 role role NN 63 65 of of IN 66 74 multiple multiple JJ 75 85 regulatory regulatory JJ 86 91 sites site NNS 91 92 . . . 94 105 Interleukin Interleukin NNP 106 107 2 2 CD 108 109 ( ( ( 109 113 IL-2 il-2 NN 113 114 ) ) ) 115 117 is be VBZ 118 120 an an DT 121 130 important important JJ 131 141 lymphokine lymphokine NN 142 150 required require VBN 151 153 in in IN 154 157 the the DT 158 165 process process NN 166 168 of of IN 169 170 T t NN 171 175 cell cell NN 176 186 activation activation NN 186 187 , , , 188 201 proliferation proliferation NN 201 202 , , , 203 209 clonal clonal JJ 210 219 expansion expansion NN 220 223 and and CC 224 239 differentiation differentiation NN 239 240 . . . 241 244 The the DT 245 249 IL-2 il-2 NN 250 254 gene gene NN 255 263 displays display VBZ 264 268 both both CC 269 270 T t NN 271 275 cell cell NN 276 284 specific specific JJ 285 288 and and CC 289 298 inducible inducible JJ 299 309 expression expression NN 309 310 : : : 311 313 it it PRP 314 316 is be VBZ 317 321 only only RB 322 331 expressed express VBN 332 334 in in IN 335 339 CD4+ cd4+ JJ 340 341 T t NN 342 347 cells cell NNS 348 353 after after IN 354 363 antigenic antigenic JJ 364 366 or or CC 367 376 mitogenic mitogenic JJ 377 388 stimulation stimulation NN 388 389 . . . 390 397 Several several JJ 398 408 cis-acting cis-acting JJ 409 419 regulatory regulatory JJ 420 425 sites site NNS 426 429 are be VBP 430 438 required require VBN 439 442 for for IN 443 452 induction induction NN 453 455 of of IN 456 459 the the DT 460 464 IL-2 il-2 NN 465 469 gene gene NN 470 475 after after IN 476 487 stimulation stimulation NN 487 488 . . . 489 491 In in IN 492 496 this this DT 497 502 study study NN 502 503 , , , 504 506 we we PRP 507 511 have have VBP 512 520 analysed analyse VBN 521 524 the the DT 525 533 function function NN 534 536 of of IN 537 542 these these DT 543 553 cis-acting cis-acting JJ 554 564 regulatory regulatory JJ 565 570 sites site NNS 571 573 in in IN 574 577 the the DT 578 585 context context NN 586 588 of of IN 589 592 the the DT 593 599 native native JJ 600 604 IL-2 il-2 NN 605 613 enhancer enhancer NN 614 617 and and CC 618 626 promoter promoter NN 627 635 sequence sequence NN 635 636 . . . 637 640 The the DT 641 648 results result NNS 649 651 of of IN 652 656 this this DT 657 662 study study NN 663 670 suggest suggest VBP 671 675 that that IN 676 679 the the DT 680 684 NFAT NFAT NNP 685 686 ( ( ( 686 690 -276 -276 CD 691 693 to to TO 694 698 -261 -261 CD 698 699 ) ) ) 699 700 , , , 701 704 the the DT 705 711 distal distal JJ 712 719 octamer octamer NN 720 721 ( ( ( 721 725 -256 -256 CD 726 728 to to TO 729 733 -248 -248 CD 733 734 ) ) ) 735 738 and and CC 739 742 the the DT 743 751 proximal proximal JJ 752 759 octamer octamer NN 760 761 ( ( ( 761 764 -75 -75 CD 765 767 to to TO 768 771 -66 -66 CD 771 772 ) ) ) 773 778 sites site NNS 779 782 not not RB 783 787 only only RB 788 791 act act VBP 792 794 as as IN 795 804 enhancers enhancer NNS 805 807 of of IN 808 812 IL-2 il-2 NN 813 817 gene gene NN 818 831 transcription transcription NN 832 834 in in IN 835 838 the the DT 839 847 presence presence NN 848 850 of of IN 851 859 cellular cellular JJ 860 871 stimulation stimulation NN 871 872 , , , 873 876 but but CC 877 881 also also RB 882 886 have have VBP 887 888 a a DT 889 898 silencing silencing JJ 899 905 effect effect NN 906 908 on on IN 909 913 IL-2 il-2 NN 914 918 gene gene NN 919 929 expression expression NN 930 932 in in IN 933 940 resting rest VBG 941 946 cells cell NNS 946 947 . . . 948 951 Two two CD 952 957 other other JJ 958 963 sites site NNS 964 971 display display VBP 972 981 disparate disparate JJ 982 989 effects effect NNS 990 992 on on IN 993 997 IL-2 il-2 NN 998 1002 gene gene NN 1003 1013 expression expression NN 1014 1016 in in IN 1017 1026 different different JJ 1027 1028 T t NN 1029 1037 leukemia leukemia NN 1038 1042 cell cell NN 1043 1048 lines line NNS 1048 1049 : : : 1050 1053 the the DT 1054 1060 distal distal JJ 1061 1067 purine purine NN 1068 1071 box box NN 1072 1073 ( ( ( 1073 1077 -291 -291 CD 1078 1080 to to TO 1081 1085 -277 -277 CD 1085 1086 ) ) ) 1087 1090 and and CC 1091 1094 the the DT 1095 1103 proximal proximal JJ 1104 1110 purine purine NN 1111 1114 box box NN 1115 1120 sites site NNS 1121 1122 ( ( ( 1122 1126 -145 -145 CD 1127 1129 to to TO 1130 1136 -128). -128). CD 1137 1144 Finally finally RB 1144 1145 , , , 1146 1149 the the DT 1150 1154 AP-1 ap-1 NN 1155 1156 ( ( ( 1156 1160 -186 -186 CD 1161 1163 to to TO 1164 1168 -176 -176 CD 1168 1169 ) ) ) 1170 1173 and and CC 1174 1177 the the DT 1178 1183 kappa kappa NN 1184 1185 B B NNP 1186 1191 sites site NNS 1192 1193 ( ( ( 1193 1197 -206 -206 CD 1198 1200 to to TO 1201 1205 -195 -195 CD 1205 1206 ) ) ) 1207 1214 respond respond VBP 1215 1217 to to TO 1218 1227 different different JJ 1228 1236 cellular cellular JJ 1237 1247 activation activation NN 1248 1250 in in IN 1251 1254 EL4 el4 NN 1255 1260 cells cell NNS 1260 1261 . . . 1262 1265 The the DT 1266 1270 AP-1 ap-1 NN 1271 1275 site site NN 1276 1284 mediated mediate VBD 1285 1288 the the DT 1289 1297 response response NN 1298 1300 to to TO 1301 1304 PMA PMA NNP 1305 1316 stimulation stimulation NN 1317 1322 while while IN 1323 1326 the the DT 1327 1332 kappa kappa NN 1333 1334 B B NNP 1335 1339 site site NN 1340 1349 responded respond VBD 1350 1352 to to TO 1353 1357 IL-1 il-1 NN 1358 1369 stimulation stimulation NN 1369 1370 . . . 1371 1376 These these DT 1377 1381 data datum NNS 1382 1389 suggest suggest VBP 1390 1394 that that IN 1395 1398 the the DT 1399 1409 regulation regulation NN 1410 1412 of of IN 1413 1417 IL-2 il-2 NN 1418 1422 gene gene NN 1423 1433 expression expression NN 1434 1436 is be VBZ 1437 1438 a a DT 1439 1446 complex complex JJ 1447 1454 process process NN 1455 1458 and and CC 1459 1467 multiple multiple JJ 1468 1478 cis-acting cis-acting JJ 1479 1489 regulatory regulatory JJ 1490 1495 sites site NNS 1496 1504 interact interact VBP 1505 1507 to to TO 1508 1513 exert exert VB 1514 1523 different different JJ 1524 1531 effects effect NNS 1532 1534 in in IN 1535 1536 T t NN 1537 1542 cells cell NNS 1543 1557 representative representative JJ 1558 1560 of of IN 1561 1572 alternative alternative JJ 1573 1579 stages stage NNS 1580 1582 of of IN 1583 1598 differentiation differentiation NN 1598 1599 . . .