0 3 The the DT 4 12 promoter promoter NN 13 16 and and CC 17 18 5 5 CD 18 19 ’ ' SYM 20 28 flanking flanking NN 29 38 sequences sequence NNS 39 50 controlling control VBG 51 56 human human JJ 57 60 B29 b29 NN 61 65 gene gene NN 66 76 expression expression NN 76 77 . . . 79 82 The the DT 83 90 product product NN 91 93 of of IN 94 97 the the DT 98 113 B-cell-specific b-cell-specific JJ 114 117 B29 b29 NN 118 122 gene gene NN 123 124 ( ( ( 124 127 B29 B29 NNP 127 128 , , , 129 131 Ig ig NN 132 136 beta beta NN 136 137 , , , 138 143 CD79b CD79b NNP 143 144 ) ) ) 145 147 is be VBZ 148 157 essential essential JJ 158 161 for for IN 162 173 Ig-mediated ig-mediated JJ 174 180 B-cell B-cell NNP 181 191 activation activation NN 192 195 via via IN 196 199 the the DT 200 206 B-cell b-cell NN 207 214 antigen antigen NN 215 223 receptor receptor NN 224 231 complex complex NN 232 233 ( ( ( 233 236 BCR BCR NNP 236 237 ) ) ) 238 240 on on IN 241 246 human human JJ 247 250 and and CC 251 257 murine murine JJ 258 259 B B NNP 260 271 lymphocytes lymphocyte NNS 271 272 . . . 273 275 To to TO 276 282 better well RBR 283 293 understand understand VB 294 297 the the DT 298 308 regulation regulation NN 309 311 of of IN 312 316 this this DT 317 324 pivotal pivotal JJ 325 329 gene gene NN 329 330 , , , 331 333 we we PRP 334 338 have have VBP 339 347 analyzed analyze VBN 348 351 the the DT 352 357 human human JJ 358 365 genomic genomic JJ 366 369 DNA dna NN 370 378 sequence sequence NN 379 387 upstream upstream JJ 388 390 of of IN 391 394 the the DT 395 398 B29 B29 NNP 399 402 ATG ATG NNP 403 408 start start NN 409 414 codon codon NN 415 418 for for IN 419 434 transcriptional transcriptional JJ 435 442 control control NN 443 451 activity activity NN 451 452 . . . 453 456 The the DT 457 462 human human JJ 463 466 B29 b29 NN 467 471 gene gene NN 472 477 lacks lack VBZ 478 484 either either CC 485 486 a a DT 487 491 TATA TATA NNP 492 494 or or CC 495 496 a a DT 497 501 CAAT CAAT NNP 502 505 box box NN 506 509 and and CC 510 523 transcription transcription NN 524 526 is be VBZ 527 536 initiated initiate VBN 537 539 at at IN 540 548 multiple multiple JJ 549 554 sites site NNS 554 555 . . . 556 559 The the DT 560 567 minimal minimal JJ 568 576 promoter promoter NN 577 579 of of IN 580 583 the the DT 584 589 human human JJ 590 593 B29 b29 NN 594 598 gene gene NN 599 601 is be VBZ 602 611 contained contain VBN 612 618 within within IN 619 620 a a DT 621 627 193-bp 193-bp JJ 628 634 region region NN 635 636 5 5 CD 636 637 ’ ' SYM 638 640 of of IN 641 646 these these DT 647 655 multiple multiple JJ 656 661 start start NN 662 667 sites site NNS 667 668 . . . 669 673 This this DT 674 681 minimal minimal JJ 682 690 promoter promoter NN 691 699 exhibits exhibit VBZ 700 715 B-cell-specific b-cell-specific JJ 716 724 activity activity NN 725 728 and and CC 729 737 contains contain VBZ 738 741 SP1 sp1 NN 741 742 , , , 743 746 ETS ETS NNP 746 747 , , , 748 751 OCT OCT NNP 751 752 , , , 753 756 and and CC 757 769 IKAROS/LYF-1 ikaros/lyf-1 NN 770 783 transcription transcription NN 784 790 factor factor NN 791 797 motifs motif NNS 797 798 . . . 799 802 All all PDT 803 808 these these DT 809 815 motifs motif NNS 816 819 are be VBP 820 830 strikingly strikingly RB 831 840 conserved conserve VBN 841 843 in in IN 844 852 sequence sequence NN 853 856 and and CC 857 866 placement placement NN 867 875 relative relative JJ 876 878 to to TO 879 882 the the DT 883 893 previously previously RB 894 907 characterized characterize VBN 908 914 murine murine JJ 915 918 B29 b29 NN 919 927 promoter promoter NN 927 928 . . . 929 939 Additional additional JJ 940 948 upstream upstream JJ 949 953 gene gene NN 954 962 segments segment NNS 963 975 dramatically dramatically RB 976 984 affected affect VBD 985 988 B29 b29 NN 989 996 minimal minimal JJ 997 1005 promoter promoter NN 1006 1014 activity activity NN 1014 1015 . . . 1016 1017 A a DT 1018 1023 newly newly RB 1024 1034 identified identify VBN 1035 1040 motif motif NN 1041 1047 called call VBN 1048 1051 the the DT 1052 1055 B29 b29 NN 1056 1065 conserved conserve VBN 1066 1074 sequence sequence NN 1075 1076 ( ( ( 1076 1079 BCS BCS NNP 1079 1080 ) ) ) 1080 1081 , , , 1082 1087 found find VBN 1088 1096 upstream upstream RB 1097 1099 of of IN 1100 1104 both both CC 1105 1110 human human JJ 1111 1114 and and CC 1115 1121 murine murine JJ 1122 1125 B29 b29 NN 1126 1135 promoters promoter NNS 1135 1136 , , , 1137 1144 appears appear VBZ 1145 1147 to to TO 1148 1157 stimulate stimulate VB 1158 1161 B29 b29 NN 1162 1175 transcription transcription NN 1176 1183 through through IN 1184 1185 a a DT 1186 1191 novel novel JJ 1192 1201 mechanism mechanism NN 1201 1202 . . . 1203 1204 A a DT 1205 1211 single single JJ 1212 1215 BCS bcs NN 1216 1219 had have VBD 1220 1226 little little JJ 1227 1233 effect effect NN 1234 1240 either either CC 1241 1243 on on IN 1244 1247 the the DT 1248 1255 minimal minimal JJ 1256 1259 B29 b29 NN 1260 1268 promoter promoter NN 1269 1271 or or CC 1272 1274 on on IN 1275 1276 a a DT 1277 1289 heterologous heterologous JJ 1290 1298 promoter promoter NN 1298 1299 . . . 1300 1307 Instead instead RB 1307 1308 , , , 1309 1312 the the DT 1313 1316 BCS bcs NN 1317 1327 stimulated stimulate VBD 1328 1341 transcription transcription NN 1342 1344 by by IN 1345 1358 counteracting counteract VBG 1359 1360 5 5 CD 1360 1361 ’ ' SYM 1362 1370 negative negative JJ 1371 1381 regulatory regulatory JJ 1382 1385 DNA dna NN 1386 1395 sequences sequence NNS 1396 1400 that that WDT 1401 1406 block block VBP 1407 1410 the the DT 1411 1419 activity activity NN 1420 1422 of of IN 1423 1426 the the DT 1427 1430 B29 b29 NN 1431 1438 minimal minimal JJ 1439 1447 promoter promoter NN 1448 1450 in in IN 1451 1454 its its PRP$ 1455 1462 absence absence NN 1462 1463 . . . 1464 1469 These these DT 1470 1478 findings finding NNS 1479 1487 indicate indicate VBP 1488 1492 that that IN 1493 1496 B29 b29 NN 1497 1501 gene gene NN 1502 1512 expression expression NN 1513 1515 is be VBZ 1516 1526 controlled control VBN 1527 1529 by by IN 1530 1533 the the DT 1534 1541 complex complex JJ 1542 1551 interplay interplay NN 1552 1554 of of IN 1555 1563 positive positive JJ 1564 1567 and and CC 1568 1576 negative negative JJ 1577 1587 regulatory regulatory JJ 1588 1596 elements element NNS 1596 1597 . . .