0 12 Coexpression coexpression NN 13 15 of of IN 16 19 the the DT 20 34 interleukin-13 interleukin-13 NN 35 38 and and CC 39 52 interleukin-4 interleukin-4 NN 53 58 genes gene NNS 59 69 correlates correlate VBZ 70 74 with with IN 75 80 their their PRP$ 81 89 physical physical JJ 90 97 linkage linkage NN 98 100 in in IN 101 104 the the DT 105 113 cytokine cytokine NN 114 118 gene gene NN 119 126 cluster cluster NN 127 129 on on IN 130 135 human human JJ 136 146 chromosome chromosome NN 147 154 5q23-31 5q23-31 NN 154 155 . . . 157 171 Interleukin-13 Interleukin-13 NNP 172 173 ( ( ( 173 178 IL-13 il-13 NN 178 179 ) ) ) 180 183 and and CC 184 188 IL-4 il-4 NN 189 192 are be VBP 193 202 cytokines cytokine NNS 203 211 produced produce VBN 212 214 by by IN 215 216 T t NN 217 222 cells cell NNS 223 227 that that WDT 228 231 are be VBP 232 239 encoded encode VBN 240 242 by by IN 243 246 the the DT 247 253 q23-31 q23-31 NN 254 260 region region NN 261 263 of of IN 264 269 human human JJ 270 280 chromosome chromosome NN 281 282 5 5 CD 282 283 . . . 284 286 To to TO 287 298 investigate investigate VB 299 302 the the DT 303 313 regulation regulation NN 314 316 of of IN 317 322 IL-13 il-13 NN 323 327 gene gene NN 328 338 expression expression NN 339 341 by by IN 342 343 T t NN 344 349 cells cell NNS 349 350 , , , 351 353 we we PRP 354 362 isolated isolate VBD 363 366 and and CC 367 376 sequenced sequence VBD 377 380 the the DT 381 386 human human JJ 387 392 IL-13 il-13 NN 393 397 gene gene NN 397 398 , , , 399 407 analyzed analyze VBD 408 411 its its PRP$ 412 423 5’-flanking 5'-flanking JJ 424 430 region region NN 431 434 for for IN 435 444 potential potential JJ 445 460 transcriptional transcriptional JJ 461 471 activation activation NN 472 480 elements element NNS 480 481 , , , 482 485 and and CC 486 494 examined examine VBD 495 498 its its PRP$ 499 509 expression expression NN 510 512 in in IN 513 527 nontransformed nontransformed JJ 528 537 T-lineage t-lineage NN 538 542 cell cell NN 543 554 populations population NNS 554 555 . . . 556 559 The the DT 560 565 human human JJ 566 571 IL-13 il-13 NN 572 576 gene gene NN 577 580 was be VBD 581 588 located located JJ 589 596 12.5-kb 12.5-kb JJ 597 605 upstream upstream NN 606 608 of of IN 609 612 the the DT 613 617 IL-4 il-4 NN 618 622 gene gene NN 623 626 and and CC 627 631 2-kb 2-kb JJ 632 642 downstream downstream RB 643 645 of of IN 646 647 a a DT 648 651 CpG CpG NNP 652 658 island island NN 658 659 . . . 660 663 The the DT 664 669 IL-13 il-13 NN 670 674 gene gene NN 675 676 5 5 CD 676 677 ’ ' SYM 678 683 flank flank NN 684 690 region region NN 691 699 included include VBD 700 701 a a DT 702 709 segment segment NN 710 714 with with IN 715 723 sequence sequence NN 724 732 homology homology NN 733 735 to to TO 736 737 P p NN 738 746 elements element NNS 747 749 of of IN 750 753 the the DT 754 758 IL-4 il-4 NN 759 767 promoter promoter NN 768 776 involved involve VBN 777 779 in in IN 780 795 transcriptional transcriptional JJ 796 806 activation activation NN 807 809 in in IN 810 811 T t NN 812 817 cells cell NNS 817 818 . . . 819 827 Mutation mutation NN 828 830 of of IN 831 834 the the DT 835 840 IL-13 il-13 NN 841 842 P p NN 843 850 element element NN 851 855 site site NN 856 869 significantly significantly RB 870 877 reduced reduce VBD 878 883 IL-13 il-13 NN 884 892 promoter promoter NN 893 901 activity activity NN 902 904 in in IN 905 913 response response NN 914 916 to to TO 917 923 T-cell t-cell NN 924 934 activation activation NN 934 935 . . . 936 952 Oligonucleotides oligonucleotide NNS 953 963 containing contain VBG 964 967 the the DT 968 973 IL-13 il-13 NN 974 976 or or CC 977 981 IL-4 il-4 NN 982 983 P p NN 984 991 element element NN 992 997 sites site NNS 998 1010 specifically specifically RB 1011 1016 bound bind VBD 1017 1020 the the DT 1021 1036 transcriptional transcriptional JJ 1037 1046 activator activator NN 1047 1054 protein protein NN 1054 1055 , , , 1056 1063 nuclear nuclear JJ 1064 1080 factor-activated factor-activated JJ 1081 1082 T t NN 1083 1088 cells cell NNS 1088 1089 , , , 1090 1099 preformed preformed JJ 1100 1101 ( ( ( 1101 1107 NF-ATp NF-ATp NNP 1107 1108 ) ) ) 1108 1109 , , , 1110 1114 when when WRB 1115 1124 incubated incubate VBN 1125 1129 with with IN 1130 1137 nuclear nuclear JJ 1138 1145 protein protein NN 1146 1154 extracts extract NNS 1155 1159 from from IN 1160 1169 activated activate VBN 1170 1171 T t NN 1172 1177 cells cell NNS 1177 1178 . . . 1179 1186 Similar similar JJ 1187 1189 to to TO 1190 1194 IL-4 il-4 NN 1194 1195 , , , 1196 1201 IL-13 IL-13 NNP 1202 1206 mRNA mrna NN 1207 1217 expression expression NN 1218 1221 was be VBD 1222 1229 highest high JJS 1230 1232 in in IN 1233 1239 T-cell t-cell NN 1240 1251 populations population NNS 1252 1260 enriched enrich VBN 1261 1264 for for IN 1265 1270 cells cell NNS 1271 1275 that that WDT 1276 1279 had have VBD 1280 1290 previously previously RB 1291 1295 been be VBN 1296 1302 primed prim VBN 1303 1305 in in FW 1306 1310 vivo vivo FW 1311 1313 or or CC 1314 1316 in in FW 1317 1322 vitro vitro FW 1322 1323 , , , 1324 1334 indicating indicate VBG 1335 1339 that that IN 1340 1347 priming priming NN 1348 1357 increases increase VBZ 1358 1361 the the DT 1362 1372 expression expression NN 1373 1375 of of IN 1376 1379 the the DT 1380 1385 IL-13 il-13 NN 1386 1389 and and CC 1390 1394 IL-4 il-4 NN 1395 1400 genes gene NNS 1401 1403 in in IN 1404 1405 a a DT 1406 1416 coordinate coordinate JJ 1417 1423 manner manner NN 1423 1424 . . . 1425 1432 Because because IN 1433 1436 the the DT 1437 1443 primed prim VBN 1444 1445 T t NN 1446 1451 cells cell NNS 1452 1459 contain contain VBP 1460 1466 higher high JJR 1467 1473 levels level NNS 1474 1476 of of IN 1477 1484 nuclear nuclear JJ 1485 1491 NF-ATp NF-ATp NNP 1491 1492 , , , 1493 1500 capable capable JJ 1501 1503 of of IN 1504 1511 binding bind VBG 1512 1514 to to TO 1515 1516 P p NN 1517 1525 elements element NNS 1526 1528 of of IN 1529 1532 the the DT 1533 1537 IL-4 il-4 NN 1538 1541 and and CC 1542 1547 IL-13 il-13 NN 1548 1557 promoters promoter NNS 1557 1558 , , , 1559 1563 than than IN 1564 1566 do do VBP 1567 1583 freshly-isolated freshly-isolated JJ 1584 1585 T t NN 1586 1591 cells cell NNS 1591 1592 , , , 1593 1596 the the DT 1597 1610 NF-AT-binding nf-at-binding JJ 1611 1612 P p NN 1613 1621 elements element NNS 1622 1625 are be VBP 1626 1636 attractive attractive JJ 1637 1647 candidates candidate NNS 1648 1650 to to TO 1651 1658 mediate mediate VB 1659 1662 the the DT 1663 1673 coordinate coordinate JJ 1674 1684 expression expression NN 1685 1687 of of IN 1688 1693 these these DT 1694 1697 two two CD 1698 1706 cytokine cytokine NN 1707 1712 genes gene NNS 1712 1713 . . .