0 8 Positive positive JJ 9 12 and and CC 13 21 negative negative JJ 22 32 regulation regulation NN 33 35 of of IN 36 50 immunoglobulin immunoglobulin NN 51 55 gene gene NN 56 66 expression expression NN 67 69 by by IN 70 71 a a DT 72 77 novel novel JJ 78 93 B-cell-specific b-cell-specific JJ 94 102 enhancer enhancer NN 103 110 element element NN 110 111 . . . 113 114 A a DT 115 118 new new JJ 119 134 B-cell-specific b-cell-specific JJ 135 143 enhancer enhancer NN 144 151 element element NN 152 155 has have VBZ 156 160 been be VBN 161 171 identified identify VBN 172 173 3 3 CD 173 174 ’ ' SYM 175 177 of of IN 178 180 E4 e4 NN 181 184 and and CC 185 188 the the DT 189 200 octamerlike octamerlike JJ 201 207 motifs motif NNS 208 210 in in IN 211 214 the the DT 215 220 human human JJ 221 235 immunoglobulin immunoglobulin NN 236 247 heavy-chain heavy-chain JJ 248 252 gene gene NN 253 261 enhancer enhancer NN 261 262 . . . 263 269 Tandem tandem JJ 270 276 copies copy NNS 277 279 of of IN 280 284 this this DT 285 290 67-bp 67-bp JJ 291 300 MnlI-AluI MnlI-AluI NNP 301 309 fragment fragment NN 309 310 , , , 311 315 when when WRB 316 321 fused fuse VBN 322 324 to to TO 325 328 the the DT 329 344 chloramphenicol chloramphenicol NN 345 362 acetyltransferase acetyltransferase NN 363 367 gene gene NN 368 374 driven drive VBN 375 377 by by IN 378 381 the the DT 382 392 conalbumin conalbumin NN 393 401 promoter promoter NN 401 402 , , , 403 413 stimulated stimulate VBD 414 427 transcription transcription NN 428 430 in in IN 431 432 B B NNP 433 438 cells cell NNS 439 442 but but CC 443 446 not not RB 447 449 in in IN 450 456 Jurkat Jurkat NNP 457 458 T t NN 459 464 cells cell NNS 465 467 or or CC 468 472 HeLa HeLa NNP 473 478 cells cell NNS 478 479 . . . 480 492 Footprinting Footprinting NNP 493 501 analysis analysis NN 502 510 revealed reveal VBD 511 515 that that IN 516 519 the the DT 520 529 identical identical JJ 530 538 sequence sequence NN 539 554 CCGAAACTGAAAAGG ccgaaactgaaaagg NN 554 555 , , , 556 566 designated designate VBN 567 569 E6 E6 NNP 569 570 , , , 571 574 was be VBD 575 584 protected protect VBN 585 587 by by IN 588 595 nuclear nuclear JJ 596 604 extracts extract NNS 605 609 from from IN 610 611 B B NNP 612 617 cells cell NNS 617 618 , , , 619 620 T t NN 621 626 cells cell NNS 626 627 , , , 628 630 or or CC 631 635 HeLa HeLa NNP 636 641 cells cell NNS 641 642 . . . 643 646 Gel Gel NNP 647 655 mobility mobility NN 656 661 shift shift NN 662 668 assays assay NNS 669 674 using use VBG 675 676 a a DT 677 686 synthetic synthetic JJ 687 689 E6 e6 NN 690 695 motif motif NN 696 704 detected detect VBD 705 706 a a DT 707 722 B-cell-specific b-cell-specific JJ 723 730 complex complex NN 731 733 in in IN 734 742 addition addition NN 743 745 to to TO 746 747 a a DT 748 758 ubiquitous ubiquitous JJ 759 763 band band NN 764 769 found find VBN 770 774 also also RB 775 777 in in IN 778 779 T t NN 780 785 cells cell NNS 786 789 and and CC 790 794 HeLa HeLa NNP 795 800 cells cell NNS 800 801 . . . 802 804 In in IN 805 814 agreement agreement NN 815 819 with with IN 820 823 the the DT 824 831 results result NNS 832 834 of of IN 835 838 gel gel NN 839 850 retardation retardation NN 851 857 assays assay NNS 857 858 , , , 859 865 tandem tandem JJ 866 872 copies copy NNS 873 875 of of IN 876 879 the the DT 880 882 E6 E6 NNP 883 888 motif motif NN 889 899 stimulated stimulate VBD 900 913 transcription transcription NN 914 916 in in IN 917 922 ARH77 ARH77 NNP 923 926 and and CC 927 931 Raji Raji NNP 932 937 cells cell NNS 938 941 but but CC 942 945 not not RB 946 948 in in IN 949 955 Jurkat Jurkat NNP 956 958 or or CC 959 963 HeLa HeLa NNP 964 969 cells cell NNS 969 970 . . . 971 982 Furthermore furthermore RB 982 983 , , , 984 985 a a DT 986 992 mutant mutant JJ 993 995 E6 e6 NN 996 1001 motif motif NN 1002 1006 lost lose VBD 1007 1011 both both CC 1012 1014 in in FW 1015 1020 vitro vitro FW 1021 1028 binding binding NN 1029 1037 activity activity NN 1038 1041 and and CC 1042 1044 in in FW 1045 1049 vivo vivo FW 1050 1058 enhancer enhancer NN 1059 1067 activity activity NN 1067 1068 . . . 1069 1071 In in IN 1072 1080 striking striking JJ 1081 1089 contrast contrast NN 1090 1092 to to TO 1093 1096 the the DT 1097 1102 mouse mouse NN 1103 1105 Ig ig NN 1106 1117 heavy-chain heavy-chain JJ 1118 1126 enhancer enhancer NN 1126 1127 , , , 1128 1130 in in IN 1131 1136 which which WDT 1137 1140 the the DT 1141 1148 octamer octamer NN 1149 1154 motif motif NN 1155 1159 acts act VBZ 1160 1162 as as IN 1163 1164 a a DT 1165 1180 B-cell-specific b-cell-specific JJ 1181 1189 enhancer enhancer NN 1190 1197 element element NN 1197 1198 , , , 1199 1202 the the DT 1203 1208 human human JJ 1209 1217 enhancer enhancer NN 1218 1226 contains contain VBZ 1227 1229 an an DT 1230 1241 octamerlike octamerlike JJ 1242 1250 sequence sequence NN 1251 1255 with with IN 1256 1259 one one CD 1260 1264 base base NN 1265 1277 substitution substitution NN 1278 1283 which which WDT 1284 1289 bound bind VBD 1290 1305 octamer-binding octamer-binding JJ 1306 1314 proteins protein NNS 1315 1319 with with IN 1320 1324 only only RB 1325 1329 very very RB 1330 1333 low low JJ 1334 1342 affinity affinity NN 1343 1346 and and CC 1347 1353 showed show VBD 1354 1356 no no DT 1357 1365 enhancer enhancer NN 1366 1374 activity activity NN 1375 1377 of of IN 1378 1381 its its PRP$ 1382 1385 own own JJ 1385 1386 . . . 1387 1400 Interestingly interestingly RB 1400 1401 , , , 1402 1405 the the DT 1406 1415 MnlI-AluI MnlI-AluI NNP 1416 1424 fragment fragment NN 1425 1430 could could MD 1431 1439 suppress suppress VB 1440 1443 the the DT 1444 1455 basal-level basal-level JJ 1456 1464 activity activity NN 1465 1467 of of IN 1468 1471 the the DT 1472 1482 conalbumin conalbumin NN 1483 1491 promoter promoter NN 1492 1494 in in IN 1495 1499 both both CC 1500 1506 Jurkat Jurkat NNP 1507 1510 and and CC 1511 1515 HeLa HeLa NNP 1516 1521 cells cell NNS 1521 1522 . . . 1523 1531 Moreover moreover RB 1531 1532 , , , 1533 1539 simian simian JJ 1540 1545 virus virus NN 1546 1548 40 40 CD 1549 1557 enhancer enhancer NN 1558 1566 activity activity NN 1567 1570 was be VBD 1571 1578 blocked block VBN 1579 1581 by by IN 1582 1585 the the DT 1586 1595 MnlI-AluI MnlI-AluI NNP 1596 1604 fragment fragment NN 1605 1607 in in IN 1608 1612 HeLa HeLa NNP 1613 1618 cells cell NNS 1619 1622 but but CC 1623 1626 not not RB 1627 1629 in in IN 1630 1631 B B NNP 1632 1637 cells cell NNS 1637 1638 . . . 1639 1643 Thus thus RB 1643 1644 , , , 1645 1648 the the DT 1649 1654 novel novel JJ 1655 1663 enhancer enhancer NN 1664 1671 element element NN 1672 1682 identified identify VBN 1683 1685 in in IN 1686 1690 this this DT 1691 1696 study study NN 1697 1699 is be VBZ 1700 1708 probably probably RB 1709 1710 a a DT 1711 1717 target target NN 1718 1722 site site NN 1723 1726 for for IN 1727 1731 both both CC 1732 1740 positive positive JJ 1741 1744 and and CC 1745 1753 negative negative JJ 1754 1761 factors factor NNS 1761 1762 . . .