0 2 An an DT 3 15 11-base-pair 11-base-pair JJ 16 19 DNA dna NN 20 28 sequence sequence NN 29 34 motif motif NN 35 45 apparently apparently RB 46 52 unique unique JJ 53 55 to to TO 56 59 the the DT 60 65 human human JJ 66 77 interleukin interleukin NN 78 79 4 4 CD 80 84 gene gene NN 85 92 confers confer VBZ 93 107 responsiveness responsiveness NN 108 110 to to TO 111 117 T-cell t-cell NN 118 128 activation activation NN 129 136 signals signal NNS 136 137 . . . 139 141 We we PRP 142 146 have have VBP 147 157 identified identify VBN 158 159 a a DT 160 163 DNA dna NN 164 171 segment segment NN 172 176 that that WDT 177 184 confers confer VBZ 185 199 responsiveness responsiveness NN 200 202 to to TO 203 210 antigen antigen NN 211 222 stimulation stimulation NN 223 230 signals signal NNS 231 233 on on IN 234 237 the the DT 238 243 human human JJ 244 255 interleukin interleukin NN 256 257 ( ( ( 257 259 IL IL NNP 259 260 ) ) ) 261 262 4 4 CD 263 267 gene gene NN 268 270 in in IN 271 277 Jurkat Jurkat NNP 278 283 cells cell NNS 283 284 . . . 285 288 The the DT 289 294 human human JJ 295 299 IL-4 il-4 NN 300 304 gene gene NN 304 305 , , , 306 308 of of IN 309 311 10 10 CD 312 321 kilobases kilobas NNS 321 322 , , , 323 325 is be VBZ 326 334 composed compose VBN 335 337 of of IN 338 342 four four CD 343 348 exons exon NNS 349 352 and and CC 353 358 three three CD 359 366 introns intron NNS 366 367 . . . 368 369 A a DT 370 380 cis-acting cis-acting JJ 381 388 element element NN 389 390 ( ( ( 390 391 P p NN 392 400 sequence sequence NN 400 401 ) ) ) 402 409 resides reside VBZ 410 412 in in IN 413 416 the the DT 417 418 5 5 CD 418 419 ’ ' SYM 420 428 upstream upstream JJ 429 435 region region NN 435 436 ; ; : 437 439 no no DT 440 450 additional additional JJ 451 454 DNA dna NN 455 463 segments segment NNS 464 468 with with IN 469 477 enhancer enhancer NN 478 486 activity activity NN 487 491 were be VBD 492 502 identified identify VBN 503 505 in in IN 506 509 the the DT 510 515 human human JJ 516 520 IL-4 il-4 NN 521 525 gene gene NN 525 526 . . . 527 530 For for IN 531 538 further further JJ 539 546 mapping mapping NN 547 555 purposes purpose NNS 555 556 , , , 557 558 a a DT 559 565 fusion fusion NN 566 574 promoter promoter NN 575 578 was be VBD 579 590 constructed construct VBN 591 595 with with IN 596 599 the the DT 600 622 granulocyte/macrophage granulocyte/macrophage JJ 623 641 colony-stimulating colony-stimulating JJ 642 648 factor factor NN 649 654 basic basic JJ 655 663 promoter promoter NN 664 674 containing contain VBG 675 677 60 60 CD 678 682 base base NN 683 688 pairs pair NNS 689 691 of of IN 692 700 sequence sequence NN 701 709 upstream upstream JJ 710 714 from from IN 715 718 the the DT 719 722 cap cap NN 723 727 site site NN 728 730 of of IN 731 734 the the DT 735 740 mouse mouse NN 741 763 granulocyte/macrophage granulocyte/macrophage JJ 764 782 colony-stimulating colony-stimulating JJ 783 789 factor factor NN 790 794 gene gene NN 795 798 and and CC 799 806 various various JJ 807 814 lengths length NNS 815 817 of of IN 818 821 the the DT 822 823 5 5 CD 823 824 ’ ' SYM 825 833 upstream upstream JJ 834 842 sequence sequence NN 843 845 of of IN 846 849 the the DT 850 854 IL-4 il-4 NN 855 859 gene gene NN 859 860 . . . 861 864 The the DT 865 866 P p NN 867 875 sequence sequence NN 876 879 was be VBD 880 887 located located JJ 888 895 between between IN 896 905 positions position NNS 906 909 -79 -79 CD 910 913 and and CC 914 917 -69 -69 CD 918 926 relative relative JJ 927 929 to to TO 930 933 the the DT 934 947 transcription transcription NN 948 953 start start NN 954 958 site site NN 959 961 of of IN 962 965 the the DT 966 971 human human JJ 972 976 IL-4 il-4 NN 977 981 gene gene NN 981 982 , , , 983 986 and and CC 987 991 this this DT 992 1000 location location NN 1001 1004 was be VBD 1005 1014 confirmed confirm VBN 1015 1017 by by IN 1018 1035 base-substitution base-substitution NN 1036 1045 mutations mutation NNS 1045 1046 . . . 1047 1050 The the DT 1051 1059 plasmids plasmid NNS 1060 1068 carrying carry VBG 1069 1077 multiple multiple JJ 1078 1084 copies copy NNS 1085 1087 of of IN 1088 1091 the the DT 1092 1093 P p NN 1094 1102 sequence sequence NN 1103 1109 showed show VBD 1110 1116 higher high JJR 1117 1131 responsiveness responsiveness NN 1132 1134 to to TO 1135 1138 the the DT 1139 1150 stimulation stimulation NN 1150 1151 . . . 1152 1155 The the DT 1156 1163 binding binding NN 1164 1174 protein(s) protein(s) NN 1175 1179 that that WDT 1180 1189 recognize recognize VBP 1190 1193 the the DT 1194 1195 P p NN 1196 1204 sequence sequence NN 1205 1207 of of IN 1208 1211 the the DT 1212 1216 IL-4 il-4 NN 1217 1221 gene gene NN 1222 1226 were be VBD 1227 1237 identified identify VBN 1238 1240 by by IN 1241 1259 DNA-mobility-shift dna-mobility-shift JJ 1260 1266 assays assay NNS 1266 1267 . . . 1268 1271 The the DT 1272 1279 binding binding NN 1280 1282 of of IN 1283 1288 NF(P) NF(P) NNP 1289 1290 ( ( ( 1290 1291 a a DT 1292 1295 DNA dna NN 1296 1303 binding binding NN 1304 1311 protein protein NN 1312 1316 that that WDT 1317 1329 specifically specifically RB 1330 1340 recognizes recognize VBZ 1341 1344 the the DT 1345 1346 P p NN 1347 1355 sequence sequence NN 1355 1356 ) ) ) 1357 1359 to to TO 1360 1363 the the DT 1364 1365 P p NN 1366 1374 sequence sequence NN 1375 1378 was be VBD 1379 1388 abolished abolish VBN 1389 1393 when when WRB 1394 1410 oligonucleotides oligonucleotide NNS 1411 1419 carrying carry VBG 1420 1424 base base NN 1425 1438 substitutions substitution NNS 1439 1443 were be VBD 1444 1448 used use VBN 1448 1449 , , , 1450 1460 indicating indicate VBG 1461 1465 that that IN 1466 1469 the the DT 1470 1475 NF(P) nf(p) NN 1476 1487 interaction interaction NN 1488 1490 is be VBZ 1491 1508 sequence-specific sequence-specific JJ 1509 1512 and and CC 1513 1517 that that IN 1518 1525 binding binding NN 1526 1537 specificity specificity NN 1538 1540 of of IN 1541 1544 the the DT 1545 1552 protein protein NN 1553 1563 paralleled parallel VBD 1564 1567 the the DT 1568 1576 sequence sequence NN 1577 1589 requirements requirement NNS 1590 1593 for for IN 1594 1598 IL-4 il-4 NN 1599 1609 expression expression NN 1610 1612 in in FW 1613 1617 vivo vivo FW 1617 1618 . . . 1619 1622 The the DT 1623 1624 P p NN 1625 1633 sequence sequence NN 1634 1638 does do VBZ 1639 1642 not not RB 1643 1648 share share VB 1649 1657 homology homology NN 1658 1662 with with IN 1663 1666 the the DT 1667 1668 5 5 CD 1668 1669 ’ ' SYM 1670 1678 upstream upstream JJ 1679 1687 sequence sequence NN 1688 1690 of of IN 1691 1694 the the DT 1695 1699 IL-2 il-2 NN 1700 1704 gene gene NN 1704 1705 , , , 1706 1710 even even RB 1711 1717 though though IN 1718 1729 surrounding surround VBG 1730 1739 sequences sequence NNS 1740 1742 of of IN 1743 1746 the the DT 1747 1751 IL-4 il-4 NN 1752 1756 gene gene NN 1757 1762 share share NN 1763 1767 high high JJ 1768 1776 homology homology NN 1777 1781 with with IN 1782 1785 the the DT 1786 1790 IL-2 il-2 NN 1791 1795 gene gene NN 1795 1796 . . . 1797 1799 We we PRP 1800 1808 conclude conclude VBP 1809 1813 that that IN 1814 1815 a a DT 1816 1825 different different JJ 1826 1829 set set NN 1830 1832 of of IN 1833 1841 proteins protein NNS 1842 1851 recognize recognize VBP 1852 1856 IL-2 il-2 NN 1857 1860 and and CC 1861 1865 IL-4 il-4 NN 1866 1871 genes gene NNS 1871 1872 . . .