0 3 The the DT 4 7 DNA dna NN 8 15 binding binding NN 16 22 domain domain NN 23 25 of of IN 26 29 the the DT 30 35 A-MYB A-MYB NNP 36 49 transcription transcription NN 50 56 factor factor NN 57 59 is be VBZ 60 71 responsible responsible JJ 72 75 for for IN 76 79 its its PRP$ 80 81 B B NNP 82 95 cell-specific cell-specific JJ 96 104 activity activity NN 105 108 and and CC 109 114 binds bind VBZ 115 117 to to TO 118 119 a a DT 120 121 B B NNP 122 126 cell cell NN 127 134 110-kDa 110-kda JJ 135 142 nuclear nuclear JJ 143 150 protein protein NN 150 151 . . . 153 163 Expression expression NN 164 171 studies study NNS 172 174 as as RB 175 179 well well RB 180 182 as as IN 183 186 the the DT 187 190 use use NN 191 193 of of IN 194 204 transgenic transgenic JJ 205 212 animals animal NNS 213 217 have have VBP 218 230 demonstrated demonstrate VBN 231 235 that that IN 236 239 the the DT 240 245 A-MYB A-MYB NNP 246 259 transcription transcription NN 260 266 factor factor NN 267 272 plays play VBZ 273 280 central central JJ 281 284 and and CC 285 293 specific specific JJ 294 298 role role NN 299 301 in in IN 302 305 the the DT 306 316 regulation regulation NN 317 319 of of IN 320 326 mature mature JJ 327 328 B B NNP 329 333 cell cell NN 334 347 proliferation proliferation NN 348 354 and/or and/or CC 355 370 differentiation differentiation NN 370 371 . . . 372 383 Furthermore furthermore RB 383 384 , , , 385 387 it it PRP 388 390 is be VBZ 391 397 highly highly RB 398 407 expressed express VBN 408 410 in in IN 411 418 Burkitt Burkitt NNP 418 420 ’s 's POS 421 429 lymphoma lymphoma NN 430 435 cells cell NNS 436 439 and and CC 440 443 may may MD 444 455 participate participate VB 456 458 in in IN 459 462 the the DT 463 475 pathogenesis pathogenesis NN 476 478 of of IN 479 483 this this DT 484 491 disease disease NN 491 492 . . . 493 495 We we PRP 496 500 have have VBP 501 510 therefore therefore RB 511 523 investigated investigate VBN 524 527 the the DT 528 543 transcriptional transcriptional JJ 544 552 activity activity NN 553 555 of of IN 556 561 A-MYB A-MYB NNP 562 565 and and CC 566 569 its its PRP$ 570 580 regulation regulation NN 581 583 in in IN 584 591 several several JJ 592 597 human human JJ 598 606 lymphoid lymphoid JJ 607 611 cell cell NN 612 617 lines line NNS 618 623 using use VBG 624 639 co-transfection co-transfection NN 640 646 assays assay NNS 647 650 and and CC 651 655 show show VBP 656 660 that that IN 661 666 A-MYB A-MYB NNP 667 669 is be VBZ 670 687 transcriptionally transcriptionally RB 688 694 active active JJ 695 697 in in IN 698 701 all all PDT 702 705 the the DT 706 707 B B NNP 708 712 cell cell NN 713 718 lines line NNS 719 726 studied study VBN 726 727 , , , 728 731 but but CC 732 735 not not RB 736 738 in in IN 739 740 T t NN 741 746 cells cell NNS 746 747 . . . 748 750 In in IN 751 761 particular particular JJ 762 765 the the DT 766 770 best good JJS 771 780 responder responder NN 781 785 cell cell NN 786 790 line line NN 791 794 was be VBD 795 798 the the DT 799 806 Burkitt Burkitt NNP 806 808 ’s 's POS 809 813 cell cell NN 814 818 line line NN 819 826 Namalwa Namalwa NNP 826 827 . . . 828 831 The the DT 832 840 activity activity NN 841 843 of of IN 844 849 A-MYB A-MYB NNP 850 852 in in IN 853 854 B B NNP 855 858 and and CC 859 862 not not RB 863 864 T t NN 865 870 cells cell NNS 871 874 was be VBD 875 883 observed observe VBN 884 888 when when WRB 889 895 either either CC 896 898 an an DT 899 909 artificial artificial JJ 910 919 construct construct NN 920 922 or or CC 923 926 the the DT 927 932 c-MYC c-myc NN 933 941 promoter promoter NN 942 945 was be VBD 946 950 used use VBN 951 953 as as IN 954 955 a a DT 956 964 reporter reporter NN 964 965 . . . 966 977 Furthermore furthermore RB 977 978 , , , 979 982 the the DT 983 993 functional functional JJ 994 1001 domains domain NNS 1002 1013 responsible responsible JJ 1014 1017 for for IN 1018 1021 DNA DNA NNP 1022 1029 binding binding NN 1029 1030 , , , 1031 1046 transactivation transactivation NN 1046 1047 , , , 1048 1051 and and CC 1052 1060 negative negative JJ 1061 1071 regulation regulation NN 1071 1072 , , , 1073 1083 previously previously RB 1084 1097 characterized characterize VBN 1098 1100 in in IN 1101 1102 a a DT 1103 1113 fibroblast fibroblast NN 1114 1121 context context NN 1121 1122 , , , 1123 1127 were be VBD 1128 1133 found find VBN 1134 1136 to to TO 1137 1141 have have VB 1142 1149 similar similar JJ 1150 1158 activity activity NN 1159 1161 in in IN 1162 1163 B B NNP 1164 1169 cells cell NNS 1169 1170 . . . 1171 1174 The the DT 1175 1181 region region NN 1182 1184 of of IN 1185 1190 A-MYB A-MYB NNP 1191 1202 responsible responsible JJ 1203 1206 for for IN 1207 1210 the the DT 1211 1212 B B NNP 1213 1217 cell cell NN 1218 1226 specific specific JJ 1227 1235 activity activity NN 1236 1239 was be VBD 1240 1247 defined define VBN 1248 1250 to to TO 1251 1253 be be VB 1254 1257 the the DT 1258 1268 N-terminal n-terminal JJ 1269 1272 218 218 CD 1273 1278 amino amino NN 1279 1284 acids acid NNS 1285 1295 containing contain VBG 1296 1299 the the DT 1300 1303 DNA dna NN 1304 1311 binding binding NN 1312 1318 domain domain NN 1318 1319 . . . 1320 1327 Finally finally RB 1327 1328 , , , 1329 1330 a a DT 1331 1338 110-kDa 110-kda JJ 1339 1346 protein protein NN 1347 1350 has have VBZ 1351 1355 been be VBN 1356 1366 identified identify VBN 1367 1369 in in IN 1370 1373 the the DT 1374 1380 nuclei nucleus NNS 1381 1383 of of IN 1384 1387 all all PDT 1388 1391 the the DT 1392 1393 B b NN 1393 1394 , , , 1395 1398 but but CC 1399 1402 not not RB 1403 1404 T t NN 1404 1405 , , , 1406 1410 cell cell NN 1411 1416 lines line NNS 1417 1421 that that WDT 1422 1434 specifically specifically RB 1435 1440 binds bind VBZ 1441 1443 to to TO 1444 1448 this this DT 1449 1454 A-MYB A-MYB NNP 1455 1465 N-terminal n-terminal JJ 1466 1472 domain domain NN 1472 1473 . . . 1474 1476 We we PRP 1477 1488 hypothesize hypothesize VBP 1489 1493 that that IN 1494 1498 this this DT 1499 1506 110-kDa 110-kda JJ 1507 1514 protein protein NN 1515 1518 may may MD 1519 1521 be be VB 1522 1523 a a DT 1524 1536 functionally functionally RB 1537 1546 important important JJ 1547 1548 B B NNP 1549 1562 cell-specific cell-specific JJ 1563 1575 co-activator co-activator NN 1576 1578 of of IN 1579 1584 A-MYB A-MYB NNP 1584 1585 . . .