0 3 The the DT 4 14 macrophage macrophage NN 15 28 transcription transcription NN 29 35 factor factor NN 36 40 PU.1 pu.1 NN 41 48 directs direct VBZ 49 64 tissue-specific tissue-specific JJ 65 75 expression expression NN 76 78 of of IN 79 82 the the DT 83 93 macrophage macrophage NN 94 112 colony-stimulating colony-stimulating JJ 113 119 factor factor NN 120 128 receptor receptor NN 128 129 . . . 131 134 The the DT 135 145 macrophage macrophage NN 146 164 colony-stimulating colony-stimulating JJ 165 171 factor factor NN 172 173 ( ( ( 173 178 M-CSF M-CSF NNP 178 179 ) ) ) 180 188 receptor receptor NN 189 191 is be VBZ 192 201 expressed express VBN 202 204 in in IN 205 206 a a DT 207 222 tissue-specific tissue-specific JJ 223 230 fashion fashion NN 231 235 from from IN 236 239 two two CD 240 248 distinct distinct JJ 249 258 promoters promoter NNS 259 261 in in IN 262 283 monocytes/macrophages monocytes/macrophage NNS 284 287 and and CC 288 291 the the DT 292 300 placenta placenta NN 300 301 . . . 302 304 In in IN 305 310 order order NN 311 313 to to TO 314 321 further further RB 322 332 understand understand VB 333 336 the the DT 337 350 transcription transcription NN 351 358 factors factor NNS 359 364 which which WDT 365 369 play play VBP 370 371 a a DT 372 376 role role NN 377 379 in in IN 380 383 the the DT 384 394 commitment commitment NN 395 397 of of IN 398 412 multipotential multipotential JJ 413 424 progenitors progenitor NNS 425 427 to to TO 428 431 the the DT 432 451 monocyte/macrophage monocyte/macrophage NN 452 459 lineage lineage NN 459 460 , , , 461 463 we we PRP 464 468 have have VBP 469 478 initiated initiate VBN 479 481 an an DT 482 495 investigation investigation NN 496 498 of of IN 499 502 the the DT 503 510 factors factor NNS 511 516 which which WDT 517 525 activate activate VBP 526 529 the the DT 530 535 M-CSF M-CSF NNP 536 544 receptor receptor NN 545 549 very very RB 550 555 early early RB 556 562 during during IN 563 566 the the DT 567 575 monocyte monocyte NN 576 591 differentiation differentiation NN 592 599 process process NN 599 600 . . . 601 605 Here here RB 606 608 we we PRP 609 620 demonstrate demonstrate VBP 621 625 that that IN 626 629 the the DT 630 635 human human JJ 636 645 monocytic monocytic JJ 646 651 M-CSF M-CSF NNP 652 660 receptor receptor NN 661 669 promoter promoter NN 670 677 directs direct VBZ 678 686 reporter reporter NN 687 691 gene gene NN 692 700 activity activity NN 701 703 in in IN 704 705 a a DT 706 721 tissue-specific tissue-specific JJ 722 729 fashion fashion NN 729 730 . . . 731 736 Since since IN 737 740 one one CD 741 743 of of IN 744 747 the the DT 748 751 few few JJ 752 765 transcription transcription NN 766 773 factors factor NNS 774 779 which which WDT 780 784 have have VBP 785 789 been be VBN 790 800 implicated implicate VBN 801 803 in in IN 804 807 the the DT 808 818 regulation regulation NN 819 821 of of IN 822 830 monocyte monocyte NN 831 836 genes gene NNS 837 839 is be VBZ 840 843 the the DT 844 855 macrophage- macrophage- NN 856 859 and and CC 860 875 B-cell-specific b-cell-specific JJ 876 880 PU.1 pu.1 NN 881 894 transcription transcription NN 895 901 factor factor NN 901 902 , , , 903 905 we we PRP 906 918 investigated investigate VBD 919 926 whether whether IN 927 931 PU.1 pu.1 NN 932 937 binds bind VBZ 938 941 and and CC 942 951 activates activate VBZ 952 955 the the DT 956 961 M-CSF M-CSF NNP 962 970 receptor receptor NN 971 979 promoter promoter NN 979 980 . . . 981 985 Here here RB 986 988 we we PRP 989 1000 demonstrate demonstrate VBP 1001 1005 that that IN 1006 1010 both both CC 1011 1013 in in IN 1014 1030 vitro-translated vitro-translated JJ 1031 1035 PU.1 pu.1 NN 1036 1039 and and CC 1040 1044 PU.1 pu.1 NN 1045 1049 from from IN 1050 1057 nuclear nuclear JJ 1058 1066 extracts extract NNS 1067 1071 bind bind VBP 1072 1074 to to TO 1075 1076 a a DT 1077 1085 specific specific JJ 1086 1090 site site NN 1091 1093 in in IN 1094 1097 the the DT 1098 1103 M-CSF M-CSF NNP 1104 1112 receptor receptor NN 1113 1121 promoter promoter NN 1122 1126 just just RB 1127 1135 upstream upstream RB 1136 1140 from from IN 1141 1144 the the DT 1145 1150 major major JJ 1151 1164 transcription transcription NN 1165 1175 initiation initiation NN 1176 1180 site site NN 1180 1181 . . . 1182 1191 Mutations mutation NNS 1192 1194 in in IN 1195 1199 this this DT 1200 1204 site site NN 1205 1210 which which WDT 1211 1220 eliminate eliminate VBP 1221 1225 PU.1 pu.1 NN 1226 1233 binding binding NN 1234 1242 decrease decrease VBP 1243 1248 M-CSF M-CSF NNP 1249 1257 receptor receptor NN 1258 1266 promoter promoter NN 1267 1275 activity activity NN 1276 1289 significantly significantly RB 1290 1292 in in IN 1293 1303 macrophage macrophage NN 1304 1308 cell cell NN 1309 1314 lines line NNS 1315 1319 only only RB 1319 1320 . . . 1321 1332 Furthermore furthermore RB 1332 1333 , , , 1334 1338 PU.1 PU.1 NNP 1339 1353 transactivates transactivate VBZ 1354 1357 the the DT 1358 1363 M-CSF M-CSF NNP 1364 1372 receptor receptor NN 1373 1381 promoter promoter NN 1382 1384 in in IN 1385 1398 nonmacrophage nonmacrophage JJ 1399 1404 cells cell NNS 1404 1405 . . . 1406 1411 These these DT 1412 1419 results result NNS 1420 1427 suggest suggest VBP 1428 1432 that that IN 1433 1437 PU.1 pu.1 NN 1438 1443 plays play VBZ 1444 1445 a a DT 1446 1451 major major JJ 1452 1456 role role NN 1457 1459 in in IN 1460 1470 macrophage macrophage NN 1471 1475 gene gene NN 1476 1486 regulation regulation NN 1487 1490 and and CC 1491 1502 development development NN 1503 1505 by by IN 1506 1515 directing direct VBG 1516 1519 the the DT 1520 1530 expression expression NN 1531 1533 of of IN 1534 1535 a a DT 1536 1544 receptor receptor NN 1545 1548 for for IN 1549 1550 a a DT 1551 1554 key key JJ 1555 1565 macrophage macrophage NN 1566 1572 growth growth NN 1573 1579 factor factor NN 1579 1580 . . .