0 3 DNA DNA NNP 4 11 triplex triplex NN 12 21 formation formation NN 22 33 selectively selectively RB 34 42 inhibits inhibit VBZ 43 65 granulocyte-macrophage granulocyte-macrophage JJ 66 84 colony-stimulating colony-stimulating JJ 85 91 factor factor NN 92 96 gene gene NN 97 107 expression expression NN 108 110 in in IN 111 116 human human JJ 117 118 T t NN 119 124 cells cell NNS 124 125 . . . 127 149 Granulocyte-macrophage granulocyte-macrophage JJ 150 168 colony-stimulating colony-stimulating JJ 169 175 factor factor NN 176 177 ( ( ( 177 183 GM-CSF GM-CSF NNP 183 184 ) ) ) 185 187 is be VBZ 188 189 a a DT 190 201 hemopoietic hemopoietic JJ 202 208 growth growth NN 209 215 factor factor NN 216 220 that that WDT 221 223 is be VBZ 224 233 expressed express VBN 234 236 in in IN 237 246 activated activate VBN 247 248 T t NN 249 254 cells cell NNS 254 255 , , , 256 267 fibroblasts fibroblast NNS 267 268 , , , 269 280 macrophages macrophage NNS 280 281 , , , 282 285 and and CC 286 297 endothelial endothelial JJ 298 303 cells cell NNS 303 304 . . . 305 313 Although although IN 314 320 GM-CSF GM-CSF NNP 321 325 does do VBZ 326 329 not not RB 330 336 appear appear VB 337 339 to to TO 340 342 be be VB 343 352 essential essential JJ 353 356 for for IN 357 363 normal normal JJ 364 375 hemopoiesis hemopoiesis NN 375 376 , , , 377 391 overexpression overexpression NN 392 394 of of IN 395 401 GM-CSF GM-CSF NNP 402 405 has have VBZ 406 410 been be VBN 411 421 implicated implicate VBN 422 424 in in IN 425 428 the the DT 429 441 pathogenesis pathogenesis NN 442 444 of of IN 445 449 some some DT 450 458 diseases disease NNS 459 463 such such JJ 464 466 as as IN 467 474 myeloid myeloid JJ 475 483 leukemia leukemia NN 484 487 and and CC 488 495 chronic chronic JJ 496 508 inflammation inflammation NN 508 509 . . . 510 512 An an DT 513 526 NF-kappaB/Rel NF-kappaB/Rel NNP 527 534 binding binding NN 535 539 site site NN 540 546 within within IN 547 550 the the DT 551 557 GM-CSF GM-CSF NNP 558 566 promoter promoter NN 566 567 , , , 568 574 termed term VBN 575 578 the the DT 579 585 kappaB kappab NN 586 593 element element NN 594 601 appears appear VBZ 602 604 to to TO 605 607 be be VB 608 617 important important JJ 618 621 for for IN 622 633 controlling control VBG 634 644 expression expression NN 645 647 in in IN 648 656 reporter reporter NN 657 661 gene gene NN 662 668 assays assay NNS 669 671 in in IN 672 680 response response NN 681 683 to to TO 684 685 a a DT 686 692 number number NN 693 695 of of IN 696 703 stimuli stimulus NNS 704 706 in in IN 707 708 T t NN 709 714 cells cell NNS 714 715 . . . 716 718 We we PRP 719 731 investigated investigate VBD 732 756 oligonucleotide-directed oligonucleotide-directed JJ 757 763 triple triple JJ 764 769 helix helix NN 770 779 formation formation NN 780 786 across across IN 787 791 this this DT 792 802 regulatory regulatory JJ 803 811 sequence sequence NN 812 814 as as IN 815 816 a a DT 817 826 potential potential JJ 827 831 tool tool NN 832 834 to to TO 835 842 inhibit inhibit VB 843 849 GM-CSF GM-CSF NNP 850 854 gene gene NN 855 868 transcription transcription NN 868 869 . . . 870 871 A a DT 872 879 15-base 15-base JJ 880 895 oligonucleotide oligonucleotide NN 895 896 , , , 897 900 GM3 GM3 NNP 900 901 , , , 902 905 was be VBD 906 914 targeted target VBN 915 917 to to TO 918 919 a a DT 920 931 purine-rich purine-rich JJ 932 938 region region NN 939 941 in in IN 942 945 the the DT 946 952 GM-CSF GM-CSF NNP 953 961 proximal proximal JJ 962 970 promoter promoter NN 970 971 , , , 972 977 which which WDT 978 986 overlaps overlap VBZ 987 990 the the DT 991 997 kappaB kappab NN 998 1005 element element NN 1005 1006 . . . 1007 1010 Gel Gel NNP 1011 1019 mobility mobility NN 1020 1025 shift shift NN 1026 1032 assays assay NNS 1033 1036 and and CC 1037 1042 DNase dnase NN 1043 1044 I i CD 1045 1057 footprinting footprinting NN 1058 1070 demonstrated demonstrate VBD 1071 1075 that that IN 1076 1079 GM3 GM3 NNP 1080 1086 formed form VBD 1087 1088 a a DT 1089 1106 sequence-specific sequence-specific JJ 1107 1116 collinear collinear JJ 1117 1124 triplex triplex NN 1125 1129 with with IN 1130 1133 its its PRP$ 1134 1149 double-stranded double-stranded JJ 1150 1153 DNA dna NN 1154 1160 target target NN 1160 1161 . . . 1162 1169 Triplex triplex NN 1170 1179 formation formation NN 1180 1182 by by IN 1183 1186 GM3 GM3 NNP 1187 1194 blocked block VBD 1195 1206 recombinant recombinant JJ 1207 1210 and and CC 1211 1218 nuclear nuclear JJ 1219 1228 NF-kappaB nf-kappab NN 1229 1237 proteins protein NNS 1238 1245 binding bind VBG 1246 1248 to to TO 1249 1252 the the DT 1253 1259 GM-CSF GM-CSF NNP 1260 1267 element element NN 1267 1268 . . . 1269 1272 GM3 GM3 NNP 1273 1277 also also RB 1278 1284 caused cause VBD 1285 1294 selective selective JJ 1295 1305 inhibition inhibition NN 1306 1308 of of IN 1309 1312 the the DT 1313 1318 human human JJ 1319 1325 T-cell t-cell NN 1326 1339 lymphotrophic lymphotrophic JJ 1340 1347 virus-1 virus-1 NN 1348 1351 Tax Tax NNP 1352 1374 transactivator-induced transactivator-induced JJ 1375 1385 luciferase luciferase NN 1386 1394 activity activity NN 1395 1399 from from IN 1400 1401 a a DT 1402 1410 reporter reporter NN 1411 1420 construct construct NN 1421 1427 driven drive VBN 1428 1430 by by IN 1431 1434 the the DT 1435 1441 GM-CSF GM-CSF NNP 1442 1450 promoter promoter NN 1451 1453 in in IN 1454 1460 Jurkat Jurkat NNP 1461 1462 T t NN 1463 1468 cells cell NNS 1468 1469 . . . 1470 1477 Finally finally RB 1477 1478 , , , 1479 1482 GM3 GM3 NNP 1483 1490 greatly greatly RB 1491 1498 reduced reduce VBD 1499 1502 the the DT 1503 1516 concentration concentration NN 1517 1519 of of IN 1520 1530 endogenous endogenous JJ 1531 1537 GM-CSF GM-CSF NNP 1538 1542 mRNA mRNA NNP 1543 1550 induced induce VBN 1551 1553 by by IN 1554 1563 different different JJ 1564 1571 stimuli stimulus NNS 1572 1574 in in IN 1575 1581 Jurkat Jurkat NNP 1582 1583 T t NN 1584 1589 cells cell NNS 1590 1593 but but CC 1594 1597 did do VBD 1598 1601 not not RB 1602 1608 affect affect VB 1609 1620 interleukin interleukin NN 1621 1622 3 3 CD 1623 1627 mRNA mrna NN 1628 1634 levels level NNS 1635 1637 in in IN 1638 1641 the the DT 1642 1646 same same JJ 1647 1652 cells cell NNS 1652 1653 . . . 1654 1656 We we PRP 1657 1665 conclude conclude VBP 1666 1670 that that IN 1671 1674 the the DT 1675 1681 kappaB kappab NN 1682 1689 element element NN 1690 1692 in in IN 1693 1696 the the DT 1697 1703 GM-CSF GM-CSF NNP 1704 1712 promoter promoter NN 1713 1718 plays play VBZ 1719 1720 a a DT 1721 1728 central central JJ 1729 1733 role role NN 1734 1736 in in IN 1737 1740 the the DT 1741 1756 transcriptional transcriptional JJ 1757 1767 activation activation NN 1768 1770 of of IN 1771 1774 the the DT 1775 1785 endogenous endogenous JJ 1786 1792 GM-CSF GM-CSF NNP 1793 1797 gene gene NN 1797 1798 . . . 1799 1807 Colinear colinear JJ 1808 1815 triplex triplex NN 1816 1825 formation formation NN 1826 1830 acts act VBZ 1831 1833 as as IN 1834 1835 a a DT 1836 1845 selective selective JJ 1846 1861 transcriptional transcriptional JJ 1862 1871 repressor repressor NN 1872 1874 of of IN 1875 1878 the the DT 1879 1885 GM-CSF GM-CSF NNP 1886 1890 gene gene NN 1891 1894 and and CC 1895 1898 may may MD 1899 1903 have have VB 1904 1913 potential potential JJ 1914 1925 therapeutic therapeutic JJ 1926 1937 application application NN 1938 1940 in in IN 1941 1946 cases case NNS 1947 1949 of of IN 1950 1961 undesirable undesirable JJ 1962 1976 overexpression overexpression NN 1977 1979 of of IN 1980 1984 this this DT 1985 1992 protein protein NN 1992 1993 . . .