0 3 Sp1 Sp1 NNP 4 6 is be VBZ 7 8 a a DT 9 17 critical critical JJ 18 24 factor factor NN 25 28 for for IN 29 32 the the DT 33 42 monocytic monocytic JJ 43 51 specific specific JJ 52 62 expression expression NN 63 65 of of IN 66 71 human human JJ 72 76 CD14 cd14 NN 76 77 . . . 79 83 CD14 cd14 NN 84 86 is be VBZ 87 88 a a DT 89 97 membrane membrane NN 98 110 glycoprotein glycoprotein NN 111 120 expressed express VBN 121 133 specifically specifically RB 134 136 on on IN 137 146 monocytes monocyte NNS 147 150 and and CC 151 162 macrophages macrophage NNS 162 163 , , , 164 167 and and CC 168 171 its its PRP$ 172 182 expression expression NN 183 185 is be VBZ 186 194 markedly markedly RB 195 204 increased increase VBN 205 211 during during IN 212 215 the the DT 216 223 process process NN 224 226 of of IN 227 235 monocyte monocyte NN 236 251 differentiation differentiation NN 251 252 . . . 253 255 In in IN 256 261 order order NN 262 264 to to TO 265 270 study study VB 271 275 CD14 cd14 NN 276 280 gene gene NN 281 291 regulation regulation NN 291 292 , , , 293 296 the the DT 297 302 human human JJ 303 307 CD14 cd14 NN 308 312 gene gene NN 313 316 was be VBD 317 323 cloned clone VBN 324 328 from from IN 329 330 a a DT 331 338 partial partial JJ 339 344 EcoRI EcoRI NNP 345 353 digested digest VBD 354 364 chromosome chromosome NN 365 366 5 5 CD 367 374 library library NN 374 375 . . . 376 377 A a DT 378 390 5.5-kilobase 5.5-kilobase JJ 391 398 genomic genomic JJ 399 404 clone clone NN 405 414 contained contain VBD 415 418 the the DT 419 430 full-length full-length JJ 431 435 CD14 cd14 NN 436 442 coding coding NN 443 451 sequence sequence NN 452 455 and and CC 456 459 4.2 4.2 CD 460 469 kilobases kilobas NNS 470 472 of of IN 473 484 5’-upstream 5'-upstream JJ 485 493 sequence sequence NN 493 494 . . . 495 498 One one CD 499 504 major major JJ 505 508 and and CC 509 512 one one CD 513 518 minor minor JJ 519 532 transcription transcription NN 533 538 start start NN 539 543 site site NN 544 548 were be VBD 549 559 identified identify VBN 560 563 101 101 CD 564 567 and and CC 568 571 130 130 CD 572 576 base base NN 577 582 pairs pair NNS 583 584 ( ( ( 584 586 bp bp NN 586 587 ) ) ) 588 596 upstream upstream RB 596 597 , , , 598 610 respectively respectively RB 610 611 , , , 612 616 from from IN 617 620 the the DT 621 628 protein protein NN 629 640 translation translation NN 641 646 start start NN 647 650 ATG ATG NNP 650 651 . . . 652 653 A a DT 654 657 DNA DNA NNP 658 666 fragment fragment NN 667 677 containing contain VBG 678 681 128 128 CD 682 684 bp bp NN 685 687 of of IN 688 696 upstream upstream JJ 697 705 sequence sequence NN 706 709 had have VBD 710 716 strong strong JJ 716 717 , , , 718 735 monocyte-specific monocyte-specific JJ 736 744 promoter promoter NN 745 753 activity activity NN 754 756 in in IN 757 760 the the DT 761 765 CD14 cd14 NN 766 774 positive positive JJ 775 784 monocytic monocytic JJ 785 789 cell cell NN 790 794 line line NN 795 799 Mono Mono NNP 800 803 Mac Mac NNP 804 805 6 6 CD 806 808 as as IN 809 817 compared compare VBN 818 820 to to TO 821 824 the the DT 825 837 nonmonocytic nonmonocytic JJ 838 842 cell cell NN 843 848 lines line NNS 849 853 HeLa HeLa NNP 854 857 and and CC 858 861 REX REX NNP 861 862 . . . 863 867 Four four CD 868 875 regions region NNS 876 878 in in IN 879 883 this this DT 884 887 DNA DNA NNP 888 896 fragment fragment NN 897 905 interact interact VBP 906 910 with with IN 911 918 nuclear nuclear JJ 919 927 proteins protein NNS 928 936 isolated isolate VBN 937 941 from from IN 942 951 monocytic monocytic JJ 952 957 cells cell NNS 957 958 . . . 959 962 The the DT 963 966 Sp1 sp1 NN 967 980 transcription transcription NN 981 987 factor factor NN 988 993 bound bind VBD 994 996 to to TO 997 1002 three three CD 1003 1012 different different JJ 1013 1020 regions region NNS 1021 1023 in in IN 1024 1027 the the DT 1028 1032 CD14 cd14 NN 1033 1041 promoter promoter NN 1041 1042 . . . 1043 1051 Mutation mutation NN 1052 1054 of of IN 1055 1058 the the DT 1059 1064 major major JJ 1065 1068 Sp1 sp1 NN 1069 1076 binding binding NN 1077 1081 site site NN 1082 1083 ( ( ( 1083 1087 -110 -110 CD 1088 1090 bp bp NN 1090 1091 ) ) ) 1092 1101 decreased decrease VBD 1102 1117 tissue-specific tissue-specific JJ 1118 1126 promoter promoter NN 1127 1135 activity activity NN 1135 1136 , , , 1137 1140 and and CC 1141 1146 these these DT 1147 1154 results result NNS 1154 1155 , , , 1156 1164 together together RB 1165 1169 with with IN 1170 1185 transactivation transactivation NN 1186 1197 experiments experiment NNS 1197 1198 , , , 1199 1210 demonstrate demonstrate VBP 1211 1215 that that IN 1216 1219 Sp1 sp1 NN 1220 1225 plays play VBZ 1226 1227 a a DT 1228 1236 critical critical JJ 1237 1241 role role NN 1242 1244 in in IN 1245 1248 the the DT 1249 1264 tissue-specific tissue-specific JJ 1265 1275 expression expression NN 1276 1278 of of IN 1279 1283 CD14 cd14 NN 1284 1286 in in IN 1287 1296 monocytic monocytic JJ 1297 1302 cells cell NNS 1302 1303 . . . 1304 1308 CD14 cd14 NN 1309 1312 Sp1 sp1 NN 1313 1317 site site NN 1318 1334 oligonucleotides oligonucleotide NNS 1335 1340 bound bind VBD 1341 1355 preferentially preferentially RB 1356 1358 to to TO 1359 1360 a a DT 1361 1368 105-kDa 105-kda JJ 1369 1372 Sp1 sp1 NN 1373 1380 species specie NNS 1380 1381 , , , 1382 1387 which which WDT 1388 1390 is be VBZ 1391 1398 present present JJ 1399 1401 in in IN 1402 1408 higher high JJR 1409 1417 relative relative JJ 1418 1424 levels level NNS 1425 1427 in in IN 1428 1437 monocytic monocytic JJ 1438 1442 than than IN 1443 1456 non-monocytic non-monocytic JJ 1457 1462 cells cell NNS 1462 1463 , , , 1464 1474 suggesting suggest VBG 1475 1479 that that IN 1480 1492 modification modification NN 1493 1495 of of IN 1496 1499 Sp1 Sp1 NNP 1499 1500 , , , 1501 1505 such such JJ 1506 1508 as as IN 1509 1524 phosphorylation phosphorylation NN 1524 1525 , , , 1526 1529 may may MD 1530 1537 explain explain VB 1538 1541 how how WRB 1542 1545 the the DT 1546 1549 Sp1 sp1 NN 1550 1554 site site NN 1555 1563 mediates mediate VBZ 1564 1573 monocytic monocytic JJ 1574 1582 specific specific JJ 1583 1591 promoter promoter NN 1592 1600 activity activity NN 1600 1601 . . .