0 7 Mapping mapping NN 8 10 of of IN 11 14 the the DT 15 26 interaction interaction NN 27 31 site site NN 32 34 of of IN 35 38 the the DT 39 48 defective defective JJ 49 62 transcription transcription NN 63 69 factor factor NN 70 72 in in IN 73 76 the the DT 77 82 class class NN 83 85 II ii CD 86 91 major major JJ 92 110 histocompatibility histocompatibility NN 111 118 complex complex NN 119 125 mutant mutant JJ 126 130 cell cell NN 131 135 line line NN 136 144 clone-13 clone-13 NN 145 147 to to TO 148 151 the the DT 152 161 divergent divergent JJ 162 168 X2-box X2-box NNP 168 169 . . . 171 173 We we PRP 174 178 have have VBP 179 189 previously previously RB 190 199 described describe VBN 200 201 a a DT 202 208 mutant mutant JJ 209 210 B B NNP 211 225 lymphoblastoid lymphoblastoid JJ 226 230 cell cell NN 231 235 line line NN 235 236 , , , 237 245 Clone-13 clone-13 NN 245 246 , , , 247 251 that that WDT 252 261 expresses express VBZ 262 268 HLA-DQ HLA-DQ NNP 269 271 in in IN 272 275 the the DT 276 283 absence absence NN 284 286 of of IN 287 293 HLA-DR HLA-DR NNP 294 297 and and CC 298 301 -DP -DP NNP 301 302 . . . 303 310 Several several JJ 311 319 criteria criterion NNS 320 329 indicated indicate VBD 330 334 that that IN 335 338 the the DT 339 345 defect defect NN 346 348 in in IN 349 353 this this DT 354 358 cell cell NN 359 363 line line NN 364 374 influences influence VBZ 375 378 the the DT 379 387 activity activity NN 388 390 of of IN 391 393 an an DT 394 410 isotype-specific isotype-specific JJ 411 424 transcription transcription NN 425 431 factor factor NN 431 432 . . . 433 439 Indeed indeed RB 439 440 , , , 441 450 transient transient JJ 451 463 transfection transfection NN 464 466 of of IN 467 474 HLA-DRA HLA-DRA NNP 475 478 and and CC 479 482 DQB DQB NNP 483 491 reporter reporter NN 492 502 constructs construct NNS 503 512 indicated indicate VBD 513 517 that that IN 518 521 the the DT 522 530 affected affect VBN 531 537 factor factor NN 538 546 operates operate VBZ 547 550 via via IN 551 563 cis-elements cis-element NNS 564 571 located located JJ 572 579 between between IN 580 584 -141 -141 CD 585 589 base base NN 590 595 pairs pair NNS 596 599 and and CC 600 603 the the DT 604 617 transcription transcription NN 618 628 initiation initiation NN 629 633 site site NN 633 634 . . . 635 636 A a DT 637 643 series series NN 644 646 of of IN 647 653 hybrid hybrid NN 654 661 DRA/DQB DRA/DQB NNP 662 670 reporter reporter NN 671 681 constructs construct NNS 682 685 was be VBD 686 695 generated generate VBN 696 698 to to TO 699 706 further further RB 707 710 map map VB 711 714 the the DT 715 723 relevant relevant JJ 724 736 cis-elements cis-element NNS 737 739 in in IN 740 744 this this DT 745 751 system system NN 751 752 . . . 753 762 Insertion insertion NN 763 765 of of IN 766 782 oligonucleotides oligonucleotide NNS 783 791 spanning span VBG 792 795 the the DT 796 799 DQB DQB NNP 800 805 X-box X-box NNP 806 807 ( ( ( 807 810 but but CC 811 814 not not RB 815 818 the the DT 819 824 DQB-W DQB-W NNP 825 831 region region NN 832 834 or or CC 835 838 the the DT 839 842 DQB DQB NNP 843 848 Y-box Y-box NNP 848 849 ) ) ) 850 858 upstream upstream RB 859 861 of of IN 862 866 -141 -141 CD 867 869 in in IN 870 871 a a DT 872 875 DRA DRA NNP 876 884 reporter reporter NN 885 892 plasmid plasmid NN 893 900 rescued rescue VBD 901 911 expression expression NN 912 914 to to TO 915 921 nearly nearly RB 922 931 wild-type wild-type JJ 932 938 levels level NNS 938 939 . . . 940 952 Substitution substitution NN 953 962 promoters promoter NNS 963 967 were be VBD 968 972 then then RB 973 982 generated generate VBN 983 988 where where WRB 989 992 the the DT 993 999 entire entire JJ 1000 1005 X-box x-box NN 1005 1006 , , , 1007 1009 or or CC 1010 1014 only only RB 1015 1018 the the DT 1019 1022 X1- X1- NNPS 1023 1025 or or CC 1026 1034 X2-boxes X2-box NNPS 1035 1037 of of IN 1038 1045 HLA-DRA HLA-DRA NNP 1046 1050 were be VBD 1051 1059 replaced replace VBN 1060 1064 with with IN 1065 1068 the the DT 1069 1078 analogous analogous JJ 1079 1086 regions region NNS 1087 1089 of of IN 1090 1097 HLA-DQB HLA-DQB NNP 1097 1098 . . . 1099 1102 The the DT 1103 1106 DQB DQB NNP 1107 1113 X2-box X2-box NNP 1114 1117 was be VBD 1118 1122 able able JJ 1123 1125 to to TO 1126 1133 restore restore VB 1134 1144 expression expression NN 1145 1147 to to TO 1148 1151 the the DT 1152 1158 silent silent JJ 1159 1162 DRA DRA NNP 1163 1171 reporter reporter NN 1172 1181 construct construct NN 1181 1182 . . . 1183 1191 Moreover moreover RB 1191 1192 , , , 1193 1204 replacement replacement NN 1205 1207 of of IN 1208 1211 the the DT 1212 1215 DQB DQB NNP 1216 1222 X2-box X2-box NNP 1223 1227 with with IN 1228 1231 the the DT 1232 1235 DRA DRA NNP 1236 1242 X2-box X2-box NNP 1243 1251 markedly markedly RB 1252 1262 diminished diminish VBD 1263 1266 the the DT 1267 1275 activity activity NN 1276 1278 of of IN 1279 1282 the the DT 1283 1286 DQB DQB NNP 1287 1295 promoter promoter NN 1296 1298 in in IN 1299 1302 the the DT 1303 1309 mutant mutant JJ 1310 1314 cell cell NN 1314 1315 . . . 1316 1320 None none NN 1321 1323 of of IN 1324 1327 the the DT 1328 1334 hybrid hybrid NN 1335 1343 reporter reporter NN 1344 1354 constructs construct NNS 1355 1359 were be VBD 1360 1369 defective defective JJ 1370 1374 when when WRB 1375 1386 transfected transfecte VBN 1387 1391 into into IN 1392 1395 the the DT 1396 1405 wild-type wild-type JJ 1405 1406 , , , 1407 1417 HLA-DR/-DQ HLA-DR/-DQ NNP 1418 1426 positive positive JJ 1427 1435 parental parental JJ 1436 1440 cell cell NN 1441 1445 line line NN 1445 1446 , , , 1447 1453 Jijoye Jijoye NNP 1453 1454 . . . 1455 1460 These these DT 1461 1468 studies study NNS 1469 1476 suggest suggest VBP 1477 1481 that that IN 1482 1485 the the DT 1486 1495 divergent divergent JJ 1496 1502 X2-box x2-box NN 1503 1505 of of IN 1506 1509 the the DT 1510 1515 class class NN 1516 1518 II ii CD 1519 1524 major major JJ 1525 1543 histocompatibility histocompatibility NN 1544 1551 complex complex NN 1552 1561 promoters promoter NNS 1562 1567 plays play VBZ 1568 1570 an an DT 1571 1580 important important JJ 1581 1585 role role NN 1586 1588 in in IN 1589 1600 influencing influence VBG 1601 1613 differential differential JJ 1614 1624 expression expression NN 1625 1627 of of IN 1628 1631 the the DT 1632 1637 human human JJ 1638 1643 class class NN 1644 1646 II ii CD 1647 1655 isotypes isotype NNS 1655 1656 . . .