0 11 Cooperation Cooperation NNP 12 14 of of IN 15 22 binding bind VBG 23 28 sites site NNS 29 32 for for IN 33 38 STAT6 STAT6 NNP 39 42 and and CC 43 45 NF NF NNP 46 51 kappa kappa NN 52 57 B/rel B/rel NNP 58 60 in in IN 61 64 the the DT 65 77 IL-4-induced il-4-induced JJ 78 91 up-regulation up-regulation NN 92 94 of of IN 95 98 the the DT 99 104 human human JJ 105 108 IgE ige NN 109 117 germline germline NN 118 126 promoter promoter NN 126 127 . . . 129 131 Ig Ig NNP 132 137 heavy heavy JJ 138 143 chain chain NN 144 149 class class NN 150 159 switching switching NN 160 162 is be VBZ 163 171 directed direct VBN 172 174 by by IN 175 184 cytokines cytokine NNS 185 193 inducing induce VBG 194 207 transcription transcription NN 208 212 from from IN 213 225 unrearranged unrearranged JJ 226 228 CH ch NN 229 234 genes gene NNS 234 235 . . . 236 248 Subsequently subsequently RB 248 249 , , , 250 254 such such JJ 255 261 primed primed JJ 262 267 cells cell NNS 268 271 can can MD 272 279 undergo undergo VB 280 286 switch switch NN 287 300 recombination recombination NN 301 303 to to TO 304 311 express express VB 312 315 the the DT 316 324 selected select VBN 325 328 new new JJ 329 336 isotype isotype NN 336 337 . . . 338 340 In in IN 341 344 the the DT 345 349 case case NN 350 352 of of IN 353 356 IgE IgE NNP 357 362 class class NN 363 372 switching switching NN 372 373 , , , 374 378 IL-4 il-4 NN 379 388 activates activate VBZ 389 392 the the DT 393 396 IgE ige NN 397 405 germline germline NN 406 414 promoter promoter NN 415 417 by by IN 418 426 inducing induce VBG 427 430 the the DT 431 442 interaction interaction NN 443 445 of of IN 446 449 the the DT 450 463 transcription transcription NN 464 470 factor factor NN 471 476 STAT6 STAT6 NNP 477 478 ( ( ( 478 486 IL-4STAT IL-4STAT NNP 486 487 ) ) ) 488 492 with with IN 493 494 a a DT 495 505 responsive responsive JJ 506 509 DNA dna NN 510 517 element element NN 518 520 in in IN 521 524 the the DT 525 533 proximal proximal JJ 534 540 region region NN 541 543 of of IN 544 547 the the DT 548 556 promoter promoter NN 556 557 . . . 558 562 This this DT 563 568 study study NN 569 578 describes describe VBZ 579 582 the the DT 583 599 characterization characterization NN 600 602 of of IN 603 606 two two CD 607 617 additional additional JJ 618 628 cis-acting cis-acting JJ 629 637 elements element NNS 638 642 that that WDT 643 651 interact interact VBP 652 656 with with IN 657 664 members member NNS 665 667 of of IN 668 671 the the DT 672 674 NF NF NNP 675 680 kappa kappa NN 681 686 B/rel B/rel NNP 687 700 transcription transcription NN 701 707 factor factor NN 708 714 family family NN 715 717 in in IN 718 720 an an DT 721 737 IL-4-independent il-4-independent JJ 738 745 fashion fashion NN 745 746 . . . 747 762 Electrophoretic electrophoretic JJ 763 771 mobility mobility NN 772 777 shift shift NN 778 784 assays assay NNS 785 789 show show VBP 790 794 that that IN 795 798 the the DT 799 812 nucleoprotein nucleoprotein NN 813 820 complex complex NN 821 827 formed form VBN 828 830 on on IN 831 834 the the DT 835 843 upstream upstream JJ 844 848 site site NN 849 850 ( ( ( 850 852 NF NF NNP 853 858 kappa kappa NN 859 861 B1 b1 NN 861 862 ) ) ) 863 871 contains contain VBZ 872 875 the the DT 876 885 classical classical JJ 886 893 p50/p65 p50/p65 NN 894 905 heterodimer heterodimer NN 905 906 . . . 907 910 The the DT 911 918 complex complex NN 919 921 on on IN 922 925 the the DT 926 934 proximal proximal JJ 935 939 site site NN 940 941 ( ( ( 941 943 NF NF NNP 944 949 kappa kappa NN 950 952 B2 b2 NN 952 953 ) ) ) 954 961 appears appear VBZ 962 964 to to TO 965 967 be be VB 968 976 composed compose VBN 977 979 of of IN 980 983 p50 p50 NN 984 987 and and CC 988 992 relB relB NNP 992 993 . . . 994 997 IgE IgE NNP 998 1006 germline germline NN 1007 1015 promoter promoter NN 1016 1024 reporter reporter NN 1025 1029 gene gene NN 1030 1040 constructs construct NNS 1041 1049 carrying carry VBG 1050 1055 point point NN 1056 1065 mutations mutation NNS 1066 1068 in in IN 1069 1072 the the DT 1073 1075 NF NF NNP 1076 1081 kappa kappa NN 1082 1084 B2 b2 NN 1085 1089 site site NN 1090 1094 were be VBD 1095 1102 largely largely RB 1103 1115 unresponsive unresponsive JJ 1116 1118 to to TO 1119 1123 IL-4 il-4 NN 1124 1135 stimulation stimulation NN 1136 1138 in in IN 1139 1148 transient transient JJ 1149 1161 transfection transfection NN 1162 1173 experiments experiment NNS 1173 1174 , , , 1175 1180 while while IN 1181 1189 plasmids plasmid NNS 1190 1194 with with IN 1195 1202 similar similar JJ 1203 1212 mutations mutation NNS 1213 1215 in in IN 1216 1219 the the DT 1220 1222 NF NF NNP 1223 1228 kappa kappa NN 1229 1231 B1 b1 NN 1232 1236 site site NN 1237 1246 responded respond VBD 1247 1249 to to TO 1250 1258 cytokine cytokine NN 1259 1270 stimulation stimulation NN 1271 1277 better well RBR 1278 1282 than than IN 1283 1286 the the DT 1287 1296 wild-type wild-type JJ 1297 1305 promoter promoter NN 1305 1306 . . . 1307 1310 The the DT 1311 1313 NF NF NNP 1314 1319 kappa kappa NN 1320 1322 B2 b2 NN 1323 1329 effect effect NN 1330 1333 was be VBD 1334 1343 dependent dependent JJ 1344 1346 on on IN 1347 1350 the the DT 1351 1359 presence presence NN 1360 1362 of of IN 1363 1366 the the DT 1367 1372 STAT6 STAT6 NNP 1373 1380 binding binding NN 1381 1385 site site NN 1385 1386 , , , 1387 1400 demonstrating demonstrate VBG 1401 1405 that that IN 1406 1409 the the DT 1410 1412 NF NF NNP 1413 1418 kappa kappa NN 1419 1421 B2 b2 NN 1422 1427 motif motif NN 1428 1430 is be VBZ 1431 1440 necessary necessary JJ 1441 1444 but but CC 1445 1448 not not RB 1449 1459 sufficient sufficient JJ 1460 1463 for for IN 1464 1473 mediating mediate VBG 1474 1482 cytokine cytokine NN 1483 1496 up-regulation up-regulation NN 1496 1497 . . . 1498 1500 In in IN 1501 1509 addition addition NN 1509 1510 , , , 1511 1514 the the DT 1515 1526 combination combination NN 1527 1529 of of IN 1530 1531 a a DT 1532 1534 NF NF NNP 1535 1540 kappa kappa NN 1541 1546 B/rel B/rel NNP 1547 1554 binding binding NN 1555 1559 site site NN 1560 1563 and and CC 1564 1567 the the DT 1568 1573 STAT6 STAT6 NNP 1574 1582 response response NN 1583 1590 element element NN 1591 1600 conferred confer VBD 1601 1605 IL-4 il-4 NN 1606 1618 inducibility inducibility NN 1619 1621 to to TO 1622 1623 a a DT 1624 1636 heterologous heterologous JJ 1637 1644 minimal minimal JJ 1645 1653 promoter promoter NN 1653 1654 , , , 1655 1660 while while IN 1661 1664 the the DT 1665 1675 individual individual JJ 1676 1681 sites site NNS 1682 1685 had have VBD 1686 1688 no no DT 1689 1695 effect effect NN 1695 1696 . . . 1697 1700 The the DT 1701 1710 available available JJ 1711 1715 data datum NNS 1716 1723 suggest suggest VBP 1724 1728 that that IN 1729 1732 the the DT 1733 1735 NF NF NNP 1736 1741 kappa kappa NN 1742 1744 B2 b2 NN 1745 1758 nucleoprotein nucleoprotein NN 1759 1766 complex complex NN 1767 1770 may may MD 1771 1780 cooperate cooperate VB 1781 1785 with with IN 1786 1795 DNA-bound dna-bound JJ 1796 1801 STAT6 stat6 NN 1802 1804 to to TO 1805 1812 achieve achieve VB 1813 1827 IL-4-dependent il-4-dependent JJ 1828 1838 activation activation NN 1839 1841 of of IN 1842 1845 the the DT 1846 1851 human human JJ 1852 1855 IgE ige NN 1856 1864 germline germline NN 1865 1869 gene gene NN 1869 1870 . . .