0 3 The the DT 4 9 human human JJ 10 24 prointerleukin prointerleukin NN 25 26 1 1 CD 27 31 beta beta NN 32 36 gene gene NN 37 45 requires require VBZ 46 49 DNA DNA NNP 50 59 sequences sequence NNS 60 64 both both CC 65 73 proximal proximal JJ 74 77 and and CC 78 84 distal distal JJ 85 87 to to TO 88 91 the the DT 92 105 transcription transcription NN 106 111 start start NN 112 116 site site NN 117 120 for for IN 121 136 tissue-specific tissue-specific JJ 137 146 induction induction NN 146 147 . . . 149 151 In in IN 152 157 these these DT 158 165 studies study NNS 165 166 , , , 167 169 we we PRP 170 174 have have VBP 175 185 identified identify VBN 186 189 DNA dna NN 190 199 sequences sequence NNS 200 203 and and CC 204 212 specific specific JJ 213 220 protein protein NN 221 233 interactions interaction NNS 234 243 necessary necessary JJ 244 247 for for IN 248 263 transcriptional transcriptional JJ 264 274 regulation regulation NN 275 277 of of IN 278 281 the the DT 282 287 human human JJ 288 302 prointerleukin prointerleukin NN 303 304 1 1 CD 305 309 beta beta NN 310 311 ( ( ( 311 318 proIL-1 proil-1 NN 319 323 beta beta NN 323 324 ) ) ) 325 329 gene gene NN 329 330 . . . 331 332 A a DT 333 354 cell-type-independent cell-type-independent JJ 355 373 lipopolysaccharide lipopolysaccharide NN 374 375 ( ( ( 375 390 LPS)-responsive lps)-responsive JJ 391 399 enhancer enhancer NN 400 407 element element NN 408 415 located located JJ 416 423 between between IN 424 429 -3757 -3757 CD 430 433 and and CC 434 439 -2729 -2729 CD 440 442 bp bp NN 443 451 upstream upstream RB 452 456 from from IN 457 460 the the DT 461 474 transcription transcription NN 475 480 start start NN 481 485 site site NN 486 487 ( ( ( 487 490 cap cap NN 491 495 site site NN 495 496 ) ) ) 497 506 consisted consist VBD 507 509 of of IN 510 512 at at IN 513 518 least least JJS 519 522 six six CD 523 531 discrete discrete JJ 532 542 subregions subregion NNS 543 548 which which WDT 549 553 were be VBD 554 563 essential essential JJ 564 566 to to TO 567 570 the the DT 571 578 maximal maximal JJ 579 588 induction induction NN 589 591 by by IN 592 595 LPS lps NN 596 598 in in IN 599 610 transfected transfecte VBN 611 620 monocytes monocyte NNS 620 621 . . . 622 625 The the DT 626 634 enhancer enhancer NN 635 639 also also RB 640 648 appeared appear VBD 649 651 to to TO 652 659 mediate mediate VB 660 667 phorbol phorbol NN 668 677 myristate myristate NN 678 685 acetate acetate NN 686 695 induction induction NN 696 698 in in IN 699 708 monocytes monocyte NNS 709 712 and and CC 713 717 IL-1 il-1 NN 718 732 responsiveness responsiveness NN 733 735 in in IN 736 747 fibroblasts fibroblast NNS 747 748 . . . 749 757 Deletion deletion NN 758 761 and and CC 762 766 base base NN 767 779 substitution substitution NN 780 789 mutations mutation NNS 790 795 along along IN 796 800 with with IN 801 804 DNA DNA NNP 805 812 binding binding NN 813 820 studies study NNS 821 833 demonstrated demonstrate VBD 834 838 that that IN 839 842 the the DT 843 851 enhancer enhancer NN 852 861 contained contain VBD 862 863 a a DT 864 871 minimum minimum NN 872 874 of of IN 875 880 three three CD 881 891 functional functional JJ 892 899 protein protein NN 900 907 binding binding NN 908 917 sequences sequence NNS 917 918 , , , 919 922 two two CD 923 925 of of IN 926 931 which which WDT 932 940 appeared appear VBD 941 943 to to TO 944 946 be be VB 947 956 important important JJ 957 960 for for IN 961 965 gene gene NN 966 975 induction induction NN 975 976 . . . 977 980 One one CD 981 983 of of IN 984 987 the the DT 988 997 essential essential JJ 998 1006 proteins protein NNS 1007 1012 which which WDT 1013 1018 bound bind VBD 1019 1021 to to TO 1022 1025 the the DT 1026 1034 enhancer enhancer NN 1035 1038 was be VBD 1039 1046 similar similar JJ 1047 1049 or or CC 1050 1059 identical identical JJ 1060 1062 to to TO 1063 1070 members member NNS 1071 1073 of of IN 1074 1077 the the DT 1078 1083 C/EBP C/EBP NNP 1084 1090 family family NN 1091 1093 of of IN 1094 1107 transcription transcription NN 1108 1115 factors factor NNS 1116 1124 required require VBN 1125 1128 for for IN 1129 1133 both both CC 1134 1139 IL-1- il-1- NN 1140 1143 and and CC 1144 1156 LPS-specific lps-specific JJ 1157 1166 induction induction NN 1167 1169 of of IN 1170 1173 the the DT 1174 1178 IL-6 il-6 NN 1179 1183 gene gene NN 1184 1185 ( ( ( 1185 1189 i.e. i.e. FW 1189 1190 , , , 1191 1194 the the DT 1195 1201 NF-IL6 NF-IL6 NNP 1202 1210 proteins protein NNS 1210 1211 ) ) ) 1211 1212 . . . 1213 1217 When when WRB 1218 1225 ligated ligate VBN 1226 1228 to to TO 1229 1232 the the DT 1233 1240 proIL-1 proil-1 NN 1241 1245 beta beta NN 1246 1249 cap cap NN 1250 1263 site-proximal site-proximal JJ 1264 1270 region region NN 1271 1272 ( ( ( 1272 1279 located located JJ 1280 1287 between between IN 1288 1292 -131 -131 CD 1293 1295 to to TO 1296 1299 +12 +12 CD 1299 1300 ) ) ) 1300 1301 , , , 1302 1306 both both CC 1307 1310 the the DT 1311 1318 proIL-1 proil-1 NN 1319 1323 beta beta NN 1324 1327 and and CC 1328 1331 the the DT 1332 1338 simian simian JJ 1339 1344 virus virus NN 1345 1347 40 40 CD 1348 1356 enhancer enhancer NN 1357 1365 elements element NNS 1366 1376 functioned function VBD 1377 1381 more more RBR 1382 1393 efficiently efficiently RB 1394 1396 in in IN 1397 1406 monocytes monocyte NNS 1407 1411 than than IN 1412 1414 in in IN 1415 1419 HeLa HeLa NNP 1420 1425 cells cell NNS 1425 1426 , , , 1427 1432 which which WDT 1433 1436 are be VBP 1437 1440 not not RB 1441 1449 normally normally RB 1450 1459 competent competent JJ 1460 1463 for for IN 1464 1468 IL-1 il-1 NN 1469 1473 beta beta NN 1474 1484 expression expression NN 1484 1485 . . . 1486 1490 When when WRB 1491 1498 ligated ligate VBN 1499 1501 to to TO 1502 1505 the the DT 1506 1512 murine murine JJ 1513 1518 c-fos c-fos NN 1519 1527 promoter promoter NN 1527 1528 , , , 1529 1536 however however RB 1536 1537 , , , 1538 1541 the the DT 1542 1549 proIL-1 proil-1 NN 1550 1554 beta beta NN 1555 1563 enhancer enhancer NN 1564 1567 was be VBD 1568 1577 inducible inducible JJ 1578 1580 in in IN 1581 1588 phorbol phorbol NN 1589 1598 myristate myristate NN 1599 1617 acetate-stimulated acetate-stimulated JJ 1618 1622 HeLa HeLa NNP 1623 1628 cells cell NNS 1628 1629 , , , 1630 1640 suggesting suggest VBG 1641 1644 the the DT 1645 1654 existence existence NN 1655 1657 of of IN 1658 1659 a a DT 1660 1667 proIL-1 proil-1 NN 1668 1672 beta beta NN 1673 1690 promoter-proximal promoter-proximal JJ 1691 1702 requirement requirement NN 1703 1706 for for IN 1707 1713 tissue tissue NN 1714 1725 specificity specificity NN 1725 1726 . . .