0 9 Synergism Synergism NNP 10 17 between between IN 18 21 two two CD 22 30 distinct distinct JJ 31 39 elements element NNS 40 42 of of IN 43 46 the the DT 47 53 HTLV-I HTLV-I NNP 54 62 enhancer enhancer NN 63 69 during during IN 70 80 activation activation NN 81 83 by by IN 84 87 the the DT 88 103 trans-activator trans-activator NN 104 106 of of IN 107 113 HTLV-I HTLV-I NNP 113 114 . . . 116 118 We we PRP 119 123 have have VBP 124 133 conducted conduct VBN 134 144 functional functional JJ 145 152 studies study NNS 153 155 of of IN 156 159 the the DT 160 168 enhancer enhancer NN 169 177 elements element NNS 178 180 of of IN 181 186 human human JJ 187 193 T-cell t-cell NN 194 202 leukemia leukemia NN 203 208 virus virus NN 209 213 type type NN 214 215 I i CD 216 217 ( ( ( 217 223 HTLV-I HTLV-I NNP 223 224 ) ) ) 225 230 using use VBG 231 234 the the DT 235 240 human human JJ 241 247 T-cell t-cell NN 248 253 lines line NNS 254 260 Jurkat Jurkat NNP 261 264 and and CC 265 269 MOLT MOLT NNP 270 271 4 4 CD 271 272 , , , 273 278 which which WDT 279 282 are be VBP 283 291 negative negative JJ 292 295 for for IN 296 302 HTLV-I HTLV-I NNP 302 303 , , , 304 307 and and CC 308 312 MT-2 MT-2 NNP 313 316 and and CC 317 323 TL-Mor TL-Mor NNP 323 324 , , , 325 330 which which WDT 331 336 carry carry VBP 337 340 the the DT 341 349 proviral proviral JJ 350 356 genome genome NN 357 359 of of IN 360 366 HTLV-I HTLV-I NNP 366 367 . . . 368 371 Two two CD 372 380 distinct distinct JJ 381 389 elements element NNS 390 394 have have VBP 395 399 been be VBN 400 410 implicated implicate VBN 411 413 in in IN 414 422 function function NN 423 425 of of IN 426 429 the the DT 430 436 HTLV-I HTLV-I NNP 437 445 enhancer enhancer NN 445 446 . . . 447 450 One one CD 451 453 is be VBZ 454 457 the the DT 458 470 21-base-pair 21-base-pair JJ 471 472 ( ( ( 472 474 bp bp NN 474 475 ) ) ) 476 480 core core NN 481 488 element element NN 489 493 that that WDT 494 496 is be VBZ 497 508 responsible responsible JJ 509 512 for for IN 513 529 trans-activation trans-activation NN 530 532 by by IN 533 536 the the DT 537 543 HTLV-I HTLV-I NNP 544 559 trans-activator trans-activator NN 560 566 p40tax p40tax NN 567 570 and and CC 571 575 that that DT 576 579 has have VBZ 580 583 the the DT 584 591 ability ability NN 592 594 to to TO 595 599 bind bind VB 600 602 to to TO 603 613 cyclic-AMP cyclic-amp NN 614 624 responsive responsive JJ 625 632 element element NN 633 640 binding binding NN 641 647 factor factor NN 648 649 ( ( ( 649 659 CREB)-like creb)-like JJ 660 669 factor(s) factor(s) NN 669 670 . . . 671 674 The the DT 675 680 other other JJ 681 683 is be VBZ 684 685 a a DT 686 692 region region NN 693 703 interposed interpose VBN 704 711 between between IN 712 715 the the DT 716 721 21-bp 21-bp JJ 722 730 elements element NNS 730 731 . . . 732 734 In in IN 735 739 this this DT 740 745 study study NN 746 748 we we PRP 749 760 demonstrate demonstrate VBP 761 765 that that IN 766 767 a a DT 768 779 subfragment subfragment NN 780 781 ( ( ( 781 784 C26 C26 NNP 784 785 ) ) ) 786 788 in in IN 789 792 the the DT 793 799 region region NN 800 807 between between IN 808 811 the the DT 812 817 21-bp 21-bp JJ 818 826 elements element NNS 827 829 is be VBZ 830 838 involved involve VBN 839 841 in in IN 842 858 trans-activation trans-activation NN 859 861 by by IN 862 868 p40tax p40tax NN 868 869 , , , 870 878 possibly possibly RB 879 886 through through IN 887 894 binding binding NN 895 897 to to TO 898 900 an an DT 901 909 NF-kappa NF-kappa NNP 910 916 B-like b-like JJ 917 924 nuclear nuclear JJ 925 931 factor factor NN 932 934 or or CC 935 942 factors factor NNS 942 943 . . . 944 953 Formation formation NN 954 956 of of IN 957 960 the the DT 961 972 protein-DNA protein-dna JJ 973 980 complex complex NN 981 985 with with IN 986 989 the the DT 990 993 C26 C26 NNP 994 1005 subfragment subfragment NN 1006 1009 was be VBD 1010 1020 positively positively RB 1021 1029 affected affect VBN 1030 1032 by by IN 1033 1039 p40tax p40tax NN 1039 1040 . . . 1041 1044 The the DT 1045 1048 C26 C26 NNP 1049 1056 element element NN 1057 1066 conferred confer VBD 1067 1074 partial partial JJ 1075 1089 responsiveness responsiveness NN 1090 1092 to to TO 1093 1099 p40tax p40tax NN 1100 1104 when when WRB 1105 1111 linked link VBN 1112 1114 to to TO 1115 1118 one one CD 1119 1123 copy copy NN 1124 1126 of of IN 1127 1130 the the DT 1131 1136 21-bp 21-bp JJ 1137 1144 element element NN 1145 1149 that that IN 1149 1150 , , , 1151 1153 by by IN 1154 1160 itself itself PRP 1160 1161 , , , 1162 1168 showed show VBD 1169 1175 little little JJ 1176 1186 activation activation NN 1187 1189 in in IN 1190 1198 response response NN 1199 1201 to to TO 1202 1208 p40tax p40tax NN 1208 1209 . . . 1210 1217 However however RB 1217 1218 , , , 1219 1222 the the DT 1223 1226 C26 C26 NNP 1227 1234 element element NN 1235 1240 alone alone RB 1240 1241 , , , 1242 1246 even even RB 1247 1251 when when WRB 1252 1260 repeated repeat VBN 1260 1261 , , , 1262 1267 could could MD 1268 1271 not not RB 1272 1274 be be VB 1275 1284 activated activate VBN 1285 1287 by by IN 1288 1294 p40tax p40tax NN 1294 1295 , , , 1296 1302 unlike unlike IN 1303 1308 other other JJ 1309 1317 NF-kappa NF-kappa NNP 1318 1327 B-binding b-binding JJ 1328 1336 elements element NNS 1336 1337 . . . 1338 1340 In in IN 1341 1349 contrast contrast NN 1349 1350 , , , 1351 1354 the the DT 1355 1358 C26 C26 NNP 1359 1366 element element NN 1367 1373 itself itself PRP 1374 1377 was be VBD 1378 1388 profoundly profoundly RB 1389 1398 activated activate VBN 1399 1403 upon upon IN 1404 1415 stimulation stimulation NN 1416 1420 with with IN 1421 1457 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate NNP 1457 1458 . . . 1459 1464 These these DT 1465 1473 findings finding NNS 1474 1483 therefore therefore RB 1484 1491 suggest suggest VBP 1492 1496 that that IN 1497 1500 the the DT 1501 1507 HTLV-I HTLV-I NNP 1508 1516 enhancer enhancer NN 1517 1525 contains contain VBZ 1526 1534 multiple multiple JJ 1535 1545 functional functional JJ 1546 1554 elements element NNS 1554 1555 , , , 1556 1565 including include VBG 1566 1573 binding bind VBG 1574 1579 sites site NNS 1580 1583 for for IN 1584 1586 at at IN 1587 1592 least least JJS 1593 1598 CREB- creb- NN 1599 1602 and and CC 1603 1611 NF-kappa NF-kappa NNP 1612 1618 B-like b-like JJ 1619 1626 factors factor NNS 1626 1627 , , , 1628 1633 which which WDT 1634 1649 synergistically synergistically RB 1650 1659 cooperate cooperate VBP 1660 1662 in in IN 1663 1673 activation activation NN 1674 1676 of of IN 1677 1680 the the DT 1681 1687 HTLV-I HTLV-I NNP 1688 1696 enhancer enhancer NN 1697 1699 in in IN 1700 1708 response response NN 1709 1711 to to TO 1712 1718 p40tax p40tax NN 1718 1719 . . . 1720 1723 Our our PRP$ 1724 1731 results result NNS 1732 1736 also also RB 1737 1748 demonstrate demonstrate VBP 1749 1753 that that IN 1754 1767 TPA-dependent tpa-dependent JJ 1768 1778 activation activation NN 1779 1781 of of IN 1782 1785 the the DT 1786 1792 HTLV-I HTLV-I NNP 1793 1801 enhancer enhancer NN 1802 1805 may may MD 1806 1808 be be VB 1809 1817 mediated mediate VBN 1818 1825 through through IN 1826 1829 the the DT 1830 1833 C26 C26 NNP 1834 1841 element element NN 1841 1842 . . .