0 4 Four four CD 5 11 P-like p-like JJ 12 20 elements element NNS 21 24 are be VBP 25 33 required require VBN 34 37 for for IN 38 45 optimal optimal JJ 46 59 transcription transcription NN 60 62 of of IN 63 66 the the DT 67 72 mouse mouse NN 73 77 IL-4 il-4 NN 78 82 gene gene NN 82 83 : : : 84 95 involvement involvement NN 96 98 of of IN 99 100 a a DT 101 109 distinct distinct JJ 110 113 set set NN 114 116 of of IN 117 124 nuclear nuclear JJ 125 131 factor factor NN 132 134 of of IN 135 144 activated activate VBN 145 146 T t NN 147 152 cells cell NNS 153 156 and and CC 157 166 activator activator NN 167 176 protein-1 protein-1 NN 177 183 family family NN 184 192 proteins protein NNS 192 193 . . . 195 197 We we PRP 198 208 previously previously RB 209 219 identified identify VBD 220 223 the the DT 224 225 P p NN 226 234 sequence sequence NN 235 237 as as IN 238 239 a a DT 240 248 critical critical JJ 249 259 regulatory regulatory JJ 260 267 element element NN 268 270 of of IN 271 274 the the DT 275 280 human human JJ 281 285 IL-4 il-4 NN 286 294 promoter promoter NN 294 295 . . . 296 298 In in IN 299 302 the the DT 303 308 mouse mouse NN 309 313 IL-4 il-4 NN 314 322 promoter promoter NN 322 323 , , , 324 329 there there EX 330 333 are be VBP 334 338 five five CD 339 347 elements element NNS 348 358 homologous homologous JJ 359 361 to to TO 362 365 the the DT 366 371 human human JJ 372 373 P p NN 374 382 sequence sequence NN 383 393 designated designate VBN 394 403 conserved conserve VBN 404 414 lymphokine lymphokine NN 415 422 element element NN 423 424 0 0 CD 425 426 ( ( ( 426 430 CLE0 CLE0 NNP 430 431 ) ) ) 431 432 , , , 433 434 P p NN 434 435 , , , 436 438 P2 P2 NNP 438 439 , , , 440 442 P3 P3 NNP 443 446 and and CC 447 449 P4 P4 NNP 449 450 . . . 451 453 To to TO 454 466 characterize characterize VB 467 470 the the DT 471 475 role role NN 476 478 of of IN 479 484 these these DT 485 491 P-like p-like JJ 492 500 elements element NNS 501 504 and and CC 505 510 their their PRP$ 511 518 binding binding NN 519 526 factors factor NNS 527 529 in in IN 530 533 the the DT 534 540 native native JJ 541 549 promoter promoter NN 549 550 , , , 551 553 we we PRP 554 557 did do VBD 558 567 transient transient JJ 568 580 transfection transfection NN 581 584 and and CC 585 600 electrophoretic electrophoretic JJ 601 609 mobility mobility NN 610 615 shift shift NN 616 622 assays assay NNS 623 624 ( ( ( 624 628 EMSA EMSA NNP 628 629 ) ) ) 629 630 . . . 631 643 Transfection transfection NN 644 646 of of IN 647 651 EL-4 el-4 NN 652 657 cells cell NNS 658 662 with with IN 663 666 the the DT 667 671 IL-4 il-4 NN 672 689 promoter-reporter promoter-reporter JJ 690 700 constructs construct NNS 701 709 carrying carry VBG 710 717 mutated mutate VBN 718 724 P-like p-like JJ 725 733 elements element NNS 734 740 showed show VBD 741 745 that that IN 746 750 four four CD 751 757 P-like p-like JJ 758 766 elements element NNS 766 767 , , , 768 772 CLE0 CLE0 NNP 772 773 , , , 774 775 P p NN 775 776 , , , 777 779 P2 p2 NN 780 783 and and CC 784 786 P4 p4 NN 786 787 , , , 788 791 but but CC 792 795 not not RB 796 798 P3 p3 NN 798 799 , , , 800 804 were be VBD 805 813 required require VBN 814 817 for for IN 818 825 optimal optimal JJ 826 836 activation activation NN 837 839 of of IN 840 843 the the DT 844 848 IL-4 il-4 NN 849 857 promoter promoter NN 857 858 . . . 859 863 EMSA EMSA NNP 864 870 showed show VBD 871 875 that that IN 876 880 both both CC 881 893 constitutive constitutive JJ 894 897 and and CC 898 907 inducible inducible JJ 908 917 complexes complex NNS 918 923 bound bind VBN 924 926 to to TO 927 931 CLE0 CLE0 NNP 931 932 , , , 933 934 P p NN 934 935 , , , 936 938 P2 p2 NN 939 942 and and CC 943 945 P4 p4 NN 945 946 , , , 947 954 whereas whereas IN 955 959 only only RB 960 961 a a DT 962 974 constitutive constitutive JJ 975 982 complex complex NN 983 988 bound bind VBD 989 991 to to TO 992 994 P3 P3 NNP 994 995 . . . 996 998 In in IN 999 1010 competition competition NN 1011 1014 and and CC 1015 1023 antibody antibody NN 1024 1034 supershift supershift NN 1035 1041 assays assay NNS 1042 1044 in in IN 1045 1049 EMSA EMSA NNP 1049 1050 , , , 1051 1060 complexes complex NNS 1061 1067 formed form VBN 1068 1072 with with IN 1073 1074 P p NN 1075 1077 or or CC 1078 1080 P2 p2 NN 1081 1087 proved prove VBD 1088 1090 to to TO 1091 1098 contain contain VB 1099 1106 nuclear nuclear JJ 1107 1113 factor factor NN 1114 1116 of of IN 1117 1126 activated activate VBN 1127 1128 T t NN 1129 1134 cells cell NNS 1135 1136 ( ( ( 1136 1140 NFAT NFAT NNP 1140 1141 ) ) ) 1142 1148 family family NN 1149 1157 proteins protein NNS 1158 1160 as as IN 1161 1166 major major JJ 1167 1177 components component NNS 1177 1178 . . . 1179 1188 Activator Activator NNP 1189 1196 protein protein NN 1197 1198 ( ( ( 1198 1203 AP)-1 ap)-1 NN 1204 1210 family family NN 1211 1219 proteins protein NNS 1220 1230 interacted interact VBD 1231 1235 with with IN 1236 1240 CLE0 CLE0 NNP 1240 1241 , , , 1242 1243 P p NN 1243 1244 , , , 1245 1247 P2 p2 NN 1248 1251 and and CC 1252 1254 P4 p4 NN 1254 1255 . . . 1256 1265 NFAT/AP-1 nfat/ap-1 NN 1266 1273 complex complex NN 1274 1280 formed form VBD 1281 1285 only only RB 1286 1290 with with IN 1291 1292 P p NN 1293 1296 and and CC 1297 1299 P2 p2 NN 1299 1300 . . . 1301 1318 Cross-competition cross-competition NN 1319 1325 assays assay NNS 1326 1331 among among IN 1332 1335 the the DT 1336 1342 P-like p-like JJ 1343 1351 elements element NNS 1352 1360 revealed reveal VBD 1361 1377 element-specific element-specific JJ 1378 1381 and and CC 1382 1388 common common JJ 1389 1398 complexes complex NNS 1398 1399 . . . 1400 1403 Six six CD 1404 1410 tandem tandem JJ 1411 1418 repeats repeat NNS 1419 1421 of of IN 1422 1425 the the DT 1426 1427 P p NN 1428 1435 element element NN 1436 1442 linked link VBN 1443 1445 to to TO 1446 1449 the the DT 1450 1454 SV40 SV40 NNP 1455 1463 promoter promoter NN 1464 1473 responded respond VBD 1474 1476 to to TO 1477 1484 phorbol phorbol NN 1485 1497 12-myristate 12-myristate NN 1498 1508 13-acetate 13-acetate NN 1508 1509 , , , 1510 1515 while while IN 1516 1520 that that DT 1521 1523 of of IN 1524 1529 other other JJ 1530 1538 elements element NNS 1539 1542 did do VBD 1543 1546 not not RB 1546 1547 . . . 1548 1550 It it PRP 1551 1556 would would MD 1557 1561 thus thus RB 1562 1568 appear appear VB 1569 1573 that that IN 1574 1584 components component NNS 1585 1587 of of IN 1588 1592 each each DT 1593 1599 P-like p-like JJ 1600 1615 element-binding element-binding JJ 1616 1625 complexes complex NNS 1626 1629 are be VBP 1630 1633 not not RB 1634 1643 identical identical JJ 1644 1647 and and CC 1648 1651 may may MD 1652 1664 coordinately coordinately RB 1665 1675 contribute contribute VB 1676 1678 to to TO 1679 1694 transcriptional transcriptional JJ 1695 1703 activity activity NN 1703 1704 . . .