0 14 Identification identification NN 15 17 of of IN 18 19 a a DT 20 26 region region NN 27 32 which which WDT 33 40 directs direct VBZ 41 44 the the DT 45 54 monocytic monocytic JJ 55 63 activity activity NN 64 66 of of IN 67 70 the the DT 71 89 colony-stimulating colony-stimulating JJ 90 96 factor factor NN 97 98 1 1 CD 99 100 ( ( ( 100 110 macrophage macrophage NN 111 129 colony-stimulating colony-stimulating JJ 130 136 factor factor NN 136 137 ) ) ) 138 146 receptor receptor NN 147 155 promoter promoter NN 156 159 and and CC 160 165 binds bind VBZ 166 175 PEBP2/CBF PEBP2/CBF NNP 176 177 ( ( ( 177 181 AML1 AML1 NNP 181 182 ) ) ) 182 183 . . . 185 188 The the DT 189 197 receptor receptor NN 198 201 for for IN 202 205 the the DT 206 216 macrophage macrophage NN 217 235 colony-stimulating colony-stimulating JJ 236 242 factor factor NN 243 244 ( ( ( 244 246 or or CC 247 265 colony-stimulating colony-stimulating JJ 266 272 factor factor NN 273 274 1 1 CD 275 276 [ [ ( 276 281 CSF-1 csf-1 NN 281 282 ] ] ) 282 283 ) ) ) 284 286 is be VBZ 287 296 expressed express VBN 297 301 from from IN 302 311 different different JJ 312 321 promoters promoter NNS 322 324 in in IN 325 334 monocytic monocytic JJ 335 340 cells cell NNS 341 344 and and CC 345 354 placental placental JJ 355 367 trophoblasts trophoblast NNS 367 368 . . . 369 371 We we PRP 372 376 have have VBP 377 389 demonstrated demonstrate VBN 390 394 that that IN 395 398 the the DT 399 416 monocyte-specific monocyte-specific JJ 417 427 expression expression NN 428 430 of of IN 431 434 the the DT 435 440 CSF-1 csf-1 NN 441 449 receptor receptor NN 450 452 is be VBZ 453 462 regulated regulate VBN 463 465 at at IN 466 469 the the DT 470 475 level level NN 476 478 of of IN 479 492 transcription transcription NN 493 495 by by IN 496 497 a a DT 498 513 tissue-specific tissue-specific JJ 514 522 promoter promoter NN 523 528 whose whose WP$ 529 537 activity activity NN 538 540 is be VBZ 541 551 stimulated stimulate VBN 552 554 by by IN 555 558 the the DT 559 583 monocyte/B-cell-specific monocyte/b-cell-specific JJ 584 597 transcription transcription NN 598 604 factor factor NN 605 609 PU.1 PU.1 NNP 610 611 ( ( ( 611 621 D.-E.Zhang D.-E.Zhang NNP 621 622 , , , 623 639 C.J.Hetherington C.J.Hetherington NNP 639 640 , , , 641 650 H.-M.Chen H.-M.Chen NNP 650 651 , , , 652 655 and and CC 656 665 D.G.Tenen D.G.Tenen NNP 665 666 , , , 667 675 Mol.Cell Mol.Cell NNP 675 676 . . . 677 692 Biol.14:373-381 Biol.14:373-381 NNP 692 693 , , , 694 698 1994 1994 CD 698 699 ) ) ) 699 700 . . . 701 705 Here here RB 706 708 we we PRP 709 715 report report VBP 716 720 that that IN 721 724 the the DT 725 731 tissue tissue NN 732 743 specificity specificity NN 744 746 of of IN 747 751 this this DT 752 760 promoter promoter NN 761 763 is be VBZ 764 768 also also RB 769 777 mediated mediate VBN 778 780 by by IN 781 790 sequences sequence NNS 791 793 in in IN 794 795 a a DT 796 802 region region NN 803 805 II ii CD 806 807 ( ( ( 807 809 bp bp NN 810 813 -88 -88 CD 814 816 to to TO 817 818 - - SYM 819 821 59 59 CD 821 822 ) ) ) 822 823 , , , 824 829 which which WDT 830 834 lies lie VBZ 835 837 10 10 CD 838 840 bp bp NN 841 849 upstream upstream RB 850 854 from from IN 855 858 the the DT 859 871 PU.1-binding pu.1-binding JJ 872 876 site site NN 876 877 . . . 878 882 When when WRB 883 891 analyzed analyze VBN 892 894 by by IN 895 900 DNase DNase NNP 901 913 footprinting footprinting NN 913 914 , , , 915 921 region region NN 922 924 II ii CD 925 928 was be VBD 929 938 protected protect VBN 939 953 preferentially preferentially RB 954 956 in in IN 957 966 monocytic monocytic JJ 967 972 cells cell NNS 972 973 . . . 974 989 Electrophoretic electrophoretic JJ 990 998 mobility mobility NN 999 1004 shift shift NN 1005 1011 assays assay NNS 1012 1021 confirmed confirm VBD 1022 1026 that that IN 1027 1033 region region NN 1034 1036 II ii CD 1037 1046 interacts interact VBZ 1047 1059 specifically specifically RB 1060 1064 with with IN 1065 1072 nuclear nuclear JJ 1073 1081 proteins protein NNS 1082 1086 from from IN 1087 1096 monocytic monocytic JJ 1097 1102 cells cell NNS 1102 1103 . . . 1104 1107 Two two CD 1108 1111 gel gel NN 1112 1117 shift shift NN 1118 1127 complexes complex NNS 1128 1129 ( ( ( 1129 1133 Mono Mono NNP 1134 1135 A A NNP 1136 1139 and and CC 1140 1144 Mono Mono NNP 1145 1146 B B NNP 1146 1147 ) ) ) 1148 1152 were be VBD 1153 1159 formed form VBN 1160 1164 with with IN 1165 1173 separate separate JJ 1174 1182 sequence sequence NN 1183 1191 elements element NNS 1192 1198 within within IN 1199 1203 this this DT 1204 1210 region region NN 1210 1211 . . . 1212 1223 Competition competition NN 1224 1227 and and CC 1228 1238 supershift supershift NN 1239 1250 experiments experiment NNS 1251 1259 indicate indicate VBP 1260 1264 that that IN 1265 1269 Mono Mono NNP 1270 1271 B B NNP 1272 1280 contains contain VBZ 1281 1282 a a DT 1283 1289 member member NN 1290 1292 of of IN 1293 1296 the the DT 1297 1309 polyomavirus polyomavirus NN 1310 1326 enhancer-binding enhancer-binding JJ 1327 1334 protein protein NN 1335 1349 2/core-binding 2/core-binding JJ 1350 1356 factor factor NN 1357 1358 ( ( ( 1358 1367 PEBP2/CBF PEBP2/CBF NNP 1367 1368 ) ) ) 1369 1375 family family NN 1375 1376 , , , 1377 1382 which which WDT 1383 1391 includes include VBZ 1392 1395 the the DT 1396 1400 AML1 aml1 NN 1401 1405 gene gene NN 1406 1413 product product NN 1413 1414 , , , 1415 1420 while while IN 1421 1425 Mono Mono NNP 1426 1427 A A NNP 1428 1430 is be VBZ 1431 1432 a a DT 1433 1441 distinct distinct JJ 1442 1449 complex complex NN 1450 1464 preferentially preferentially RB 1465 1474 expressed express VBN 1475 1477 in in IN 1478 1487 monocytic monocytic JJ 1488 1493 cells cell NNS 1493 1494 . . . 1495 1503 Promoter promoter NN 1504 1514 constructs construct NNS 1515 1519 with with IN 1520 1529 mutations mutation NNS 1530 1532 in in IN 1533 1538 these these DT 1539 1547 sequence sequence NN 1548 1556 elements element NNS 1557 1561 were be VBD 1562 1564 no no RB 1565 1571 longer longer RBR 1572 1581 expressed express VBN 1582 1594 specifically specifically RB 1595 1597 in in IN 1598 1607 monocytes monocyte NNS 1607 1608 . . . 1609 1620 Furthermore furthermore RB 1620 1621 , , , 1622 1634 multimerized multimerized JJ 1635 1641 region region NN 1642 1644 II ii CD 1645 1653 sequence sequence NN 1654 1662 elements element NNS 1663 1671 enhanced enhance VBD 1672 1675 the the DT 1676 1684 activity activity NN 1685 1687 of of IN 1688 1689 a a DT 1690 1702 heterologous heterologous JJ 1703 1712 thymidine thymidine NN 1713 1719 kinase kinase NNP 1720 1728 promoter promoter NN 1729 1731 in in IN 1732 1741 monocytic monocytic JJ 1742 1747 cells cell NNS 1748 1751 but but CC 1752 1755 not not RB 1756 1761 other other JJ 1762 1766 cell cell NN 1767 1772 types type NNS 1773 1779 tested test VBN 1779 1780 . . . 1781 1786 These these DT 1787 1794 results result NNS 1795 1803 indicate indicate VBP 1804 1808 that that IN 1809 1812 the the DT 1813 1837 monocyte/B-cell-specific monocyte/b-cell-specific JJ 1838 1851 transcription transcription NN 1852 1858 factor factor NN 1859 1863 PU.1 pu.1 NN 1864 1867 and and CC 1868 1871 the the DT 1872 1876 Mono Mono NNP 1877 1878 A A NNP 1879 1882 and and CC 1883 1887 Mono Mono NNP 1888 1889 B B NNP 1890 1897 protein protein NN 1898 1907 complexes complex NNS 1908 1911 act act VBP 1912 1914 in in IN 1915 1922 concert concert NN 1923 1925 to to TO 1926 1934 regulate regulate VB 1935 1952 monocyte-specific monocyte-specific JJ 1953 1966 transcription transcription NN 1967 1969 of of IN 1970 1973 the the DT 1974 1979 CSF-1 csf-1 NN 1980 1988 receptor receptor NN 1988 1989 . . .