0 10 Regulation regulation NN 11 13 of of IN 14 17 the the DT 18 24 tissue tissue NN 25 31 factor factor NN 32 36 gene gene NN 37 39 in in IN 40 45 human human JJ 46 55 monocytic monocytic JJ 56 61 cells cell NNS 61 62 . . . 63 67 Role role NN 68 70 of of IN 71 75 AP-1 ap-1 NN 75 76 , , , 77 85 NF-kappa NF-kappa NNP 86 91 B/Rel B/Rel NNP 91 92 , , , 93 96 and and CC 97 100 Sp1 sp1 NN 101 109 proteins protein NNS 110 112 in in IN 113 122 uninduced uninduced JJ 123 126 and and CC 127 153 lipopolysaccharide-induced lipopolysaccharide-induced JJ 154 164 expression expression NN 164 165 . . . 167 173 Tissue tissue NN 174 180 factor factor NN 181 182 ( ( ( 182 184 TF TF NNP 184 185 ) ) ) 186 196 expression expression NN 197 199 by by IN 200 210 peripheral peripheral JJ 211 216 blood blood NN 217 226 monocytes monocyte NNS 227 233 during during IN 234 240 sepsis sepsis NN 241 250 initiates initiate VBZ 251 264 intravascular intravascular JJ 265 275 thrombosis thrombosis NN 275 276 . . . 277 286 Bacterial bacterial JJ 287 305 lipopolysaccharide lipopolysaccharide NN 306 307 ( ( ( 307 310 LPS LPS NNP 310 311 ) ) ) 312 319 rapidly rapidly RB 320 327 induces induce VBZ 328 330 TF TF NNP 331 335 gene gene NN 336 349 transcription transcription NN 350 352 in in IN 353 362 monocytes monocyte NNS 362 363 . . . 364 367 The the DT 368 373 human human JJ 374 376 TF tf NN 377 385 promoter promoter NN 386 394 contains contain VBZ 395 402 binding bind VBG 403 408 sites site NNS 409 412 for for IN 413 416 the the DT 417 430 transcription transcription NN 431 438 factors factor NNS 439 443 AP-1 ap-1 NN 443 444 , , , 445 454 c-Rel/p65 c-rel/p65 NN 454 455 , , , 456 461 Egr-1 Egr-1 NNP 461 462 , , , 463 466 and and CC 467 470 Sp1 Sp1 NNP 470 471 . . . 472 480 NF-kappa NF-kappa NNP 481 486 B/Rel B/Rel NNP 487 495 proteins protein NNS 496 500 have have VBP 501 505 been be VBN 506 511 shown show VBN 512 514 to to TO 515 525 physically physically RB 526 534 interact interact VB 535 539 with with IN 540 544 both both CC 545 549 AP-1 ap-1 NN 550 553 and and CC 554 557 Sp1 sp1 NN 558 566 proteins protein NNS 566 567 . . . 568 570 In in IN 571 575 this this DT 576 581 study study NN 581 582 , , , 583 585 we we PRP 586 598 investigated investigate VBD 599 602 the the DT 603 607 role role NN 608 610 of of IN 611 616 these these DT 617 630 transcription transcription NN 631 638 factors factor NNS 639 641 in in IN 642 651 uninduced uninduced JJ 652 655 and and CC 656 667 LPS-induced lps-induced JJ 668 670 TF TF NNP 671 675 gene gene NN 676 686 expression expression NN 687 689 in in IN 690 695 human human JJ 696 705 monocytic monocytic JJ 706 711 THP-1 thp-1 NN 712 717 cells cell NNS 717 718 . . . 719 729 Deletional deletional JJ 730 738 analysis analysis NN 739 748 indicated indicate VBD 749 753 that that IN 754 758 five five CD 759 762 Sp1 sp1 NN 763 768 sites site NNS 769 777 mediated mediate VBD 778 783 basal basal JJ 784 794 expression expression NN 795 797 in in IN 798 807 uninduced uninduced JJ 808 813 cells cell NNS 813 814 . . . 815 818 The the DT 819 822 two two CD 823 827 AP-1 ap-1 NN 828 833 sites site NNS 834 839 bound bind VBD 840 851 c-Fos/c-Jun c-fos/c-jun NN 852 864 heterodimers heterodimer NNS 865 867 in in IN 868 872 both both CC 873 885 unstimulated unstimulated JJ 886 889 and and CC 890 904 LPS-stimulated lps-stimulated JJ 905 910 cells cell NNS 910 911 . . . 912 919 Maximal maximal JJ 920 923 LPS LPS NNP 924 933 induction induction NN 934 936 of of IN 937 940 the the DT 941 943 TF TF NNP 944 952 promoter promoter NN 953 961 required require VBD 962 965 the the DT 966 969 two two CD 970 974 AP-1 ap-1 NN 975 980 sites site NNS 981 984 and and CC 985 988 the the DT 989 994 kappa kappa NN 995 996 B B NNP 997 1001 site site NN 1002 1008 within within IN 1009 1012 the the DT 1013 1016 LPS LPS NNP 1017 1025 response response NN 1026 1033 element element NN 1033 1034 . . . 1035 1045 Disruption disruption NN 1046 1048 of of IN 1049 1052 the the DT 1053 1062 conserved conserve VBN 1063 1070 spacing spacing NN 1071 1078 between between IN 1079 1082 the the DT 1083 1091 proximal proximal JJ 1092 1096 AP-1 ap-1 NN 1097 1101 site site NN 1102 1105 and and CC 1106 1109 the the DT 1110 1115 kappa kappa NN 1116 1117 B B NNP 1118 1122 site site NN 1123 1132 abolished abolish VBD 1133 1136 LPS LPS NNP 1137 1146 induction induction NN 1146 1147 . . . 1148 1159 Replacement replacement NN 1160 1162 of of IN 1163 1166 the the DT 1167 1170 two two CD 1171 1175 AP-1 ap-1 NN 1176 1181 sites site NNS 1182 1186 with with IN 1187 1200 intrinsically intrinsically RB 1201 1205 bent bent JJ 1206 1209 DNA dna NN 1210 1219 partially partially RB 1220 1228 restored restore VBD 1229 1232 LPS LPS NNP 1233 1242 induction induction NN 1242 1243 , , , 1244 1254 suggesting suggest VBG 1255 1257 an an DT 1258 1268 additional additional JJ 1269 1279 structural structural JJ 1280 1284 role role NN 1285 1288 for for IN 1289 1292 the the DT 1293 1297 AP-1 ap-1 NN 1298 1303 sites site NNS 1303 1304 . . . 1305 1316 Synergistic synergistic JJ 1317 1332 transactivation transactivation NN 1333 1335 of of IN 1336 1339 the the DT 1340 1343 LPS LPS NNP 1344 1352 response response NN 1353 1360 element element NN 1361 1363 in in IN 1364 1374 Drosophila drosophila FW 1375 1384 Schneider Schneider NNP 1385 1390 cells cell NNS 1391 1393 by by IN 1394 1406 coexpression coexpression NN 1407 1409 of of IN 1410 1415 c-Fos c-fos NN 1415 1416 , , , 1417 1422 c-Jun c-jun NN 1422 1423 , , , 1424 1429 c-Rel c-rel NN 1429 1430 , , , 1431 1434 and and CC 1435 1438 p65 p65 NN 1439 1441 or or CC 1442 1447 c-Jun c-jun NN 1448 1451 and and CC 1452 1455 p65 p65 NN 1456 1464 required require VBD 1465 1468 the the DT 1469 1484 transactivation transactivation NN 1485 1492 domains domain NNS 1493 1495 of of IN 1496 1501 c-Jun c-jun NN 1502 1505 and and CC 1506 1509 p65 p65 NN 1509 1510 . . . 1511 1516 These these DT 1517 1521 data datum NNS 1522 1531 indicated indicate VBD 1532 1536 that that IN 1537 1548 c-Fos/c-Jun c-fos/c-jun NN 1548 1549 , , , 1550 1559 c-Rel/p65 c-rel/p65 NN 1559 1560 , , , 1561 1564 and and CC 1565 1568 Sp1 Sp1 NNP 1569 1577 regulate regulate VBP 1578 1580 TF TF NNP 1581 1585 gene gene NN 1586 1596 expression expression NN 1597 1599 in in IN 1600 1605 human human JJ 1606 1615 monocytic monocytic JJ 1616 1621 cells cell NNS 1621 1622 . . .