0 12 Differential differential JJ 13 24 interaction interaction NN 25 27 of of IN 28 35 nuclear nuclear JJ 36 43 factors factor NNS 44 48 with with IN 49 52 the the DT 53 58 PRE-I PRE-I NNP 59 67 enhancer enhancer NN 68 75 element element NN 76 78 of of IN 79 82 the the DT 83 88 human human JJ 89 93 IL-4 il-4 NN 94 102 promoter promoter NN 103 105 in in IN 106 115 different different JJ 116 117 T t NN 118 122 cell cell NN 123 130 subsets subset NNS 130 131 . . . 133 136 The the DT 137 153 immunomodulatory immunomodulatory JJ 154 162 cytokine cytokine NN 163 167 IL-4 il-4 NN 168 175 affects affect VBZ 176 181 cells cell NNS 182 184 of of IN 185 189 most most JJS 190 201 hemopoietic hemopoietic JJ 202 210 lineages lineage NNS 210 211 . . . 212 216 IL-4 il-4 NN 217 219 is be VBZ 220 228 secreted secrete VBN 229 231 by by IN 232 241 activated activate VBN 242 245 Th2 th2 NN 246 249 but but CC 250 253 not not RB 254 257 Th1 th1 NN 258 263 cells cell NNS 264 267 and and CC 268 273 plays play VBZ 274 275 a a DT 276 281 major major JJ 282 286 role role NN 287 289 in in IN 290 293 the the DT 294 300 immune immune JJ 301 309 response response NN 310 312 by by IN 313 323 modulating modulate VBG 324 327 the the DT 328 343 differentiation differentiation NN 344 346 of of IN 347 352 naive naive JJ 353 355 Th th NN 356 361 cells cell NNS 362 368 toward toward IN 369 372 the the DT 373 376 Th2 th2 NN 377 386 phenotype phenotype NN 386 387 . . . 388 390 We we PRP 391 395 have have VBP 396 406 previously previously RB 407 417 identified identify VBN 418 420 an an DT 421 429 enhancer enhancer NN 430 437 element element NN 437 438 , , , 439 444 PRE-I PRE-I NNP 444 445 , , , 446 450 that that WDT 451 453 is be VBZ 454 463 essential essential JJ 464 467 for for IN 468 471 the the DT 472 480 function function NN 481 483 of of IN 484 487 the the DT 488 493 human human JJ 494 498 IL-4 il-4 NN 499 507 promoter promoter NN 507 508 . . . 509 511 To to TO 512 523 investigate investigate VB 524 527 the the DT 528 538 mechanisms mechanism NNS 539 550 responsible responsible JJ 551 554 for for IN 555 570 tissue-specific tissue-specific JJ 571 581 expression expression NN 582 584 of of IN 585 588 the the DT 589 593 IL-4 il-4 NN 594 598 gene gene NN 598 599 , , , 600 602 we we PRP 603 611 analyzed analyze VBD 612 619 nuclear nuclear JJ 620 627 factors factor NNS 628 635 binding bind VBG 636 638 to to TO 639 642 the the DT 643 648 PRE-I PRE-I NNP 649 653 site site NN 654 657 and and CC 658 666 compared compare VBD 667 670 the the DT 671 678 binding binding NN 679 689 activities activity NNS 690 692 of of IN 693 698 these these DT 699 706 factors factor NNS 707 709 to to TO 710 713 the the DT 714 718 IL-4 il-4 NN 719 727 promoter promoter NN 728 730 of of IN 731 734 Th1 th1 NN 735 738 and and CC 739 742 Th2 th2 NN 743 748 cells cell NNS 748 749 . . . 750 752 We we PRP 753 757 show show VBP 758 762 that that IN 763 768 PRE-I PRE-I NNP 769 778 interacts interact VBZ 779 783 with with IN 784 788 PMA- PMA- NNP 789 792 and and CC 793 816 PMA/ionomycin-inducible pma/ionomycin-inducible JJ 816 817 , , , 818 829 cyclosporin cyclosporin NN 830 841 A-sensitive a-sensitive JJ 842 849 nuclear nuclear JJ 850 857 factors factor NNS 857 858 . . . 859 864 Using use VBG 865 879 anti-C/EBPbeta anti-c/ebpbeta JJ 880 881 ( ( ( 881 887 NF-IL6 NF-IL6 NNP 887 888 ) ) ) 888 889 , , , 890 905 anti-C/EBPdelta anti-c/ebpdelta JJ 906 907 ( ( ( 907 917 NF-IL6beta NF-IL6beta NNP 917 918 ) ) ) 918 919 , , , 920 931 anti-NF-ATc anti-nf-atc JJ 931 932 , , , 933 944 anti-NF-ATp anti-nf-atp JJ 944 945 , , , 946 954 anti-Fos anti-fos JJ 954 955 , , , 956 959 and and CC 960 968 anti-Jun anti-jun JJ 969 972 Abs ab NNS 973 975 we we PRP 976 987 demonstrate demonstrate VBP 988 992 that that IN 993 996 the the DT 997 1007 previously previously RB 1008 1018 identified identify VBN 1019 1024 PRE-I PRE-I NNP 1025 1032 binding binding NN 1033 1039 factor factor NN 1040 1045 POS-1 pos-1 NN 1046 1048 is be VBZ 1049 1057 composed compose VBN 1058 1060 of of IN 1061 1070 different different JJ 1071 1084 transcription transcription NN 1085 1092 factors factor NNS 1093 1095 in in IN 1096 1105 different different JJ 1106 1108 Th Th NNP 1109 1113 cell cell NN 1114 1121 subsets subset NNS 1121 1122 . . . 1123 1125 In in IN 1126 1129 the the DT 1130 1144 IL-4-producing il-4-producing JJ 1145 1153 Th0-like th0-like JJ 1154 1159 human human JJ 1160 1166 Jurkat jurkat NN 1167 1170 and and CC 1171 1176 mouse mouse NN 1177 1181 EL-4 el-4 NN 1182 1187 cells cell NNS 1187 1188 , , , 1189 1194 POS-1 POS-1 NNP 1195 1196 ( ( ( 1196 1206 designated designate VBN 1207 1213 POS-1a POS-1a NNP 1213 1214 ) ) ) 1215 1223 contains contain VBZ 1224 1234 NF-IL6beta NF-IL6beta NNP 1235 1238 and and CC 1239 1242 Jun Jun NNP 1242 1243 . . . 1244 1246 In in IN 1247 1250 the the DT 1251 1256 mouse mouse NN 1257 1260 Th2 th2 NN 1261 1264 D10 d10 NN 1265 1270 cells cell NNS 1271 1274 and and CC 1275 1277 in in IN 1278 1281 the the DT 1282 1287 human human JJ 1288 1291 Th2 th2 NN 1292 1298 clones clone NNS 1298 1299 , , , 1300 1305 POS-1 POS-1 NNP 1306 1307 ( ( ( 1307 1317 designated designate VBN 1318 1324 POS-1b POS-1b NNP 1324 1325 ) ) ) 1326 1334 contains contain VBZ 1335 1345 NF-IL6beta NF-IL6beta NNP 1345 1346 , , , 1347 1350 Jun Jun NNP 1350 1351 , , , 1352 1355 and and CC 1356 1364 NF-ATc/p NF-ATc/p NNP 1364 1365 . . . 1366 1368 In in IN 1369 1377 contrast contrast NN 1377 1378 , , , 1379 1384 POS-1 POS-1 NNP 1385 1388 was be VBD 1389 1392 not not RB 1393 1398 found find VBN 1399 1401 in in IN 1402 1409 nuclear nuclear JJ 1410 1418 extracts extract NNS 1419 1421 of of IN 1422 1427 human human JJ 1428 1431 Th1 th1 NN 1432 1438 clones clone NNS 1438 1439 . . . 1440 1445 These these DT 1446 1454 findings finding NNS 1455 1462 suggest suggest VBP 1463 1467 that that IN 1468 1473 PRE-I PRE-I NNP 1474 1477 may may MD 1478 1482 play play VB 1483 1484 a a DT 1485 1489 role role NN 1490 1492 in in IN 1493 1496 the the DT 1497 1509 differential differential JJ 1510 1520 regulation regulation NN 1521 1523 of of IN 1524 1528 IL-4 il-4 NN 1529 1533 gene gene NN 1534 1544 expression expression NN 1545 1551 levels level NNS 1551 1552 . . .