0 1 c c SYM 1 2 - - : 2 5 Maf Maf NNP 6 13 induces induce VBZ 14 23 monocytic monocytic JJ 24 39 differentiation differentiation NN 40 43 and and CC 44 53 apoptosis apoptosis NN 54 56 in in IN 57 65 bipotent bipotent JJ 66 73 myeloid myeloid JJ 74 85 progenitors progenitor NNS 85 86 . . . 88 91 The the DT 92 107 transcriptional transcriptional JJ 108 118 mechanisms mechanism NNS 119 123 that that WDT 124 129 drive drive VBP 130 144 colony-forming colony-forming JJ 145 149 unit unit NN 150 172 granulocyte-macrophage granulocyte-macrophage NN 173 174 ( ( ( 174 180 CFU-GM CFU-GM NNP 180 181 ) ) ) 182 189 myeloid myeloid JJ 190 201 progenitors progenitor NNS 202 204 to to TO 205 218 differentiate differentiate VB 219 223 into into IN 224 229 cells cell NNS 230 232 of of IN 233 239 either either CC 240 243 the the DT 244 256 granulocytic granulocytic JJ 257 259 or or CC 260 269 monocytic monocytic JJ 270 277 lineage lineage NN 278 281 are be VBP 282 285 not not RB 286 291 fully fully RB 292 302 understood understand VBN 302 303 . . . 304 306 We we PRP 307 311 have have VBP 312 317 shown show VBN 318 322 that that IN 323 326 the the DT 327 332 c-Maf c-maf NN 333 336 and and CC 337 342 c-Myb c-myb NN 343 356 transcription transcription NN 357 364 factors factor NNS 365 375 physically physically RB 376 384 interact interact VBP 385 387 in in IN 388 395 myeloid myeloid JJ 396 401 cells cell NNS 402 404 to to TO 405 409 form form VB 410 420 inhibitory inhibitory JJ 421 430 complexes complex NNS 431 435 that that WDT 436 442 hinder hinder VBP 443 458 transactivation transactivation NN 459 461 of of IN 462 467 c-Myb c-myb NN 468 474 target target NN 475 480 genes gene NNS 481 488 through through IN 489 495 direct direct JJ 496 503 binding binding NN 504 506 to to TO 507 510 Myb Myb NNP 511 520 consensus consensus NN 521 526 sites site NNS 526 527 . . . 528 533 These these DT 534 543 complexes complex NNS 544 549 arise arise VBP 550 552 in in IN 553 554 a a DT 555 570 developmentally developmentally RB 571 580 regulated regulate VBN 581 588 pattern pattern NN 588 589 , , , 590 597 peaking peak VBG 598 600 at at IN 601 604 the the DT 605 617 promyelocyte promyelocyte JJ 618 623 stage stage NN 623 624 , , , 625 627 or or CC 628 630 in in IN 631 635 cell cell NN 636 641 model model NN 642 649 systems system NNS 649 650 , , , 651 660 appearing appear VBG 661 665 soon soon RB 666 671 after after IN 672 675 the the DT 676 685 induction induction NN 686 688 of of IN 689 698 monocytic monocytic JJ 699 714 differentiation differentiation NN 714 715 . . . 716 718 We we PRP 719 725 wished wish VBD 726 728 to to TO 729 738 determine determine VB 739 741 if if IN 742 746 this this DT 747 762 developmentally developmentally RB 763 770 related related JJ 771 782 interaction interaction NN 783 785 is be VBZ 786 787 a a DT 788 799 consequence consequence NN 800 802 of of IN 803 810 myeloid myeloid JJ 811 826 differentiation differentiation NN 827 829 or or CC 830 832 an an DT 833 842 intrinsic intrinsic JJ 843 858 differentiating differentiate VBG 859 867 stimulus stimulus NN 867 868 . . . 869 876 Because because IN 877 880 the the DT 881 889 elevated elevated JJ 890 897 Myb:Maf Myb:Maf NNP 898 904 status status NN 905 909 seen see VBN 910 912 in in IN 913 928 differentiating differentiate VBG 929 934 cells cell NNS 935 938 can can MD 939 941 be be VB 942 955 recapitulated recapitulate VBN 956 958 by by IN 959 973 overexpression overexpression NN 974 976 of of IN 977 982 c-Maf c-maf NN 983 985 in in IN 986 993 myeloid myeloid JJ 994 998 cell cell NN 999 1004 lines line NNS 1004 1005 , , , 1006 1008 we we PRP 1009 1018 inducibly inducibly RB 1019 1028 expressed express VBD 1029 1032 the the DT 1033 1038 c-Maf c-maf NN 1039 1043 cDNA cdna NN 1044 1046 in in IN 1047 1048 2 2 CD 1049 1057 bipotent bipotent JJ 1058 1063 human human JJ 1064 1071 myeloid myeloid JJ 1072 1082 progenitor progenitor NN 1083 1088 cells cell NNS 1088 1089 . . . 1090 1098 Elevated elevated JJ 1099 1105 levels level NNS 1106 1108 of of IN 1109 1114 c-Maf c-maf NN 1115 1122 protein protein NN 1123 1126 led lead VBD 1127 1129 to to TO 1130 1136 marked marked JJ 1137 1146 increases increase NNS 1147 1149 in in IN 1150 1157 Myb:Maf Myb:Maf NNP 1158 1167 complexes complex NNS 1168 1171 and and CC 1172 1175 the the DT 1176 1188 accumulation accumulation NN 1189 1191 of of IN 1192 1211 monocyte/macrophage monocyte/macrophage NN 1212 1217 cells cell NNS 1217 1218 , , , 1219 1227 followed follow VBN 1228 1230 by by IN 1231 1239 eventual eventual JJ 1240 1250 programmed program VBN 1251 1255 cell cell NN 1256 1261 death death NN 1261 1262 . . . 1263 1271 Analysis Analysis NNP 1272 1274 of of IN 1275 1282 targets target NNS 1283 1287 that that WDT 1288 1293 could could MD 1294 1301 mediate mediate VB 1302 1307 these these DT 1308 1318 phenotypic phenotypic JJ 1319 1326 changes change NNS 1327 1336 indicated indicate VBD 1337 1341 that that IN 1342 1347 c-Maf c-maf NN 1348 1354 likely likely RB 1355 1360 plays play VBZ 1361 1362 a a DT 1363 1366 key key JJ 1367 1371 role role NN 1372 1374 in in IN 1375 1382 myeloid myeloid JJ 1383 1387 cell cell NN 1388 1399 development development NN 1400 1407 through through IN 1408 1412 dual dual JJ 1413 1423 mechanisms mechanism NNS 1423 1424 ; ; : 1425 1435 inhibition inhibition NN 1436 1438 of of IN 1439 1440 a a DT 1441 1447 select select JJ 1448 1451 set set NN 1452 1454 of of IN 1455 1460 c-Myb c-myb NN 1461 1470 regulated regulated JJ 1471 1478 targets target NNS 1478 1479 , , , 1480 1484 such such JJ 1485 1487 as as IN 1488 1493 Bcl-2 Bcl-2 NNP 1494 1497 and and CC 1498 1506 CD13/APN CD13/APN NNP 1506 1507 , , , 1508 1515 coupled couple VBN 1516 1520 with with IN 1521 1524 the the DT 1525 1535 activation activation NN 1536 1538 of of IN 1539 1541 as as RB 1542 1545 yet yet RB 1546 1555 undefined undefined JJ 1556 1581 differentiation-promoting differentiation-promoting JJ 1582 1587 genes gene NNS 1587 1588 . . .