0 11 DNA-binding dna-binding JJ 12 19 studies study NNS 20 22 of of IN 23 26 the the DT 27 39 Epstein-Barr epstein-barr JJ 40 45 virus virus NN 46 53 nuclear nuclear JJ 54 61 antigen antigen NN 62 63 2 2 CD 64 65 ( ( ( 65 71 EBNA-2 ebna-2 NN 71 72 ) ) ) 72 73 : : : 74 82 evidence evidence NN 83 86 for for IN 87 94 complex complex NN 95 104 formation formation NN 105 107 by by IN 108 114 latent latent JJ 115 123 membrane membrane NN 124 131 protein protein NN 132 136 gene gene NN 137 153 promoter-binding promoter-binding JJ 154 162 proteins protein NNS 163 165 in in IN 166 181 EBNA-2-positive ebna-2-positive JJ 182 186 cell cell NN 187 192 lines line NNS 192 193 . . . 195 198 The the DT 199 211 Epstein-Barr epstein-barr JJ 212 217 virus virus NN 218 219 ( ( ( 219 222 EBV EBV NNP 222 223 ) ) ) 224 231 nuclear nuclear JJ 232 239 antigen antigen NN 240 241 2 2 CD 242 243 ( ( ( 243 249 EBNA-2 ebna-2 NN 249 250 ) ) ) 251 258 protein protein NN 259 261 is be VBZ 262 271 essential essential JJ 272 275 for for IN 276 279 the the DT 280 295 immortalization immortalization NN 296 298 of of IN 299 304 human human JJ 305 312 primary primary JJ 313 314 B b NN 315 320 cells cell NNS 321 323 by by IN 324 327 EBV EBV NNP 327 328 . . . 329 335 EBNA-2 ebna-2 NN 336 351 trans-activates trans-activate VBZ 352 360 cellular cellular JJ 361 364 and and CC 365 370 viral viral JJ 371 376 genes gene NNS 377 381 like like IN 382 386 CD23 CD23 NNP 386 387 , , , 388 393 c-fgr c-fgr NN 393 394 , , , 395 401 latent latent JJ 402 410 membrane membrane NN 411 418 protein protein NN 419 420 1 1 CD 421 422 ( ( ( 422 426 LMP1 lmp1 NN 426 427 ) ) ) 428 431 and and CC 432 440 terminal terminal JJ 441 448 protein protein NN 449 450 1 1 CD 451 452 ( ( ( 452 455 TP1 tp1 NN 455 456 ) ) ) 456 457 . . . 458 474 Trans-activation Trans-activation NNP 475 477 of of IN 478 481 the the DT 482 485 TP1 tp1 NN 486 494 promoter promoter NN 495 498 and and CC 499 501 of of IN 502 505 the the DT 506 511 BamHI BamHI NNP 512 513 C C NNP 514 522 promoter promoter NN 523 526 has have VBZ 527 534 already already RB 535 539 been be VBN 540 552 investigated investigate VBN 553 555 in in IN 556 562 detail detail NN 563 566 and and CC 567 574 appears appear VBZ 575 577 to to TO 578 580 be be VB 581 589 mediated mediate VBN 590 593 via via IN 594 609 protein-protein protein-protein JJ 610 622 interactions interaction NNS 623 626 and and CC 627 630 not not RB 631 633 by by IN 634 640 direct direct JJ 641 648 binding binding NN 649 651 of of IN 652 658 EBNA-2 ebna-2 NN 659 663 type type NN 664 665 A A NNP 666 667 ( ( ( 667 669 of of IN 670 673 EBV EBV NNP 674 678 type type NN 679 680 1 1 CD 680 681 ) ) ) 682 684 to to TO 685 688 the the DT 689 692 DNA dna NN 692 693 . . . 694 700 EBNA-2 ebna-2 NN 701 703 is be VBZ 704 708 able able JJ 709 711 to to TO 712 726 trans-activate trans-activate VB 727 730 the the DT 731 741 expression expression NN 742 744 of of IN 745 748 the the DT 749 752 LMP LMP NNP 753 757 gene gene NN 758 760 in in IN 761 768 several several JJ 769 773 cell cell NN 774 779 lines line NNS 779 780 . . . 781 788 Various various JJ 789 796 reports report NNS 797 801 have have VBP 802 812 delineated delineate VBN 813 816 the the DT 817 827 cis-acting cis-acting JJ 828 836 elements element NNS 837 839 of of IN 840 843 the the DT 844 847 LMP LMP NNP 848 856 promoter promoter NN 857 864 through through IN 865 870 which which WDT 871 877 EBNA-2 ebna-2 NN 878 886 mediates mediate VBZ 887 903 trans-activation trans-activation NN 903 904 . . . 905 907 To to TO 908 917 determine determine VB 918 925 whether whether IN 926 932 EBNA-2 ebna-2 NN 933 937 also also RB 938 953 trans-activates trans-activate VBZ 954 957 the the DT 958 961 LMP LMP NNP 962 970 promoter promoter NN 971 973 by by IN 974 989 protein-protein protein-protein JJ 990 1002 interactions interaction NNS 1002 1003 , , , 1004 1006 we we PRP 1007 1016 performed perform VBD 1017 1018 a a DT 1019 1025 series series NN 1026 1028 of of IN 1029 1032 gel gel NN 1033 1044 retardation retardation NN 1045 1051 assays assay NNS 1052 1055 and and CC 1056 1067 competition competition NN 1068 1079 experiments experiment NNS 1080 1084 with with IN 1085 1088 LMP LMP NNP 1089 1097 promoter promoter NN 1098 1107 fragments fragment NNS 1108 1110 of of IN 1111 1120 different different JJ 1121 1126 sizes size NNS 1126 1127 . . . 1128 1130 We we PRP 1131 1141 determined determine VBD 1142 1146 that that IN 1147 1150 the the DT 1151 1166 protein-binding protein-binding JJ 1167 1173 region region NN 1174 1176 on on IN 1177 1180 the the DT 1181 1184 LMP LMP NNP 1185 1193 promoter promoter NN 1194 1197 was be VBD 1198 1204 within within IN 1205 1206 a a DT 1207 1209 42 42 CD 1210 1212 bp bp NN 1213 1221 fragment fragment NN 1222 1234 encompassing encompass VBG 1235 1246 nucleotides nucleotide NNS 1247 1251 -135 -135 CD 1252 1254 to to TO 1255 1259 -176 -176 CD 1260 1268 relative relative JJ 1269 1271 to to TO 1272 1275 the the DT 1276 1279 LMP LMP NNP 1280 1295 transcriptional transcriptional JJ 1296 1301 start start NN 1302 1306 site site NN 1306 1307 . . . 1308 1312 None none NN 1313 1315 of of IN 1316 1319 the the DT 1320 1323 DNA dna NN 1324 1333 fragments fragment NNS 1334 1346 investigated investigate VBN 1347 1356 indicated indicate VBD 1357 1368 interaction interaction NN 1369 1371 of of IN 1372 1378 EBNA-2 ebna-2 NN 1379 1383 with with IN 1384 1387 the the DT 1388 1391 DNA dna NN 1392 1395 via via IN 1396 1411 protein-protein protein-protein JJ 1412 1424 interactions interaction NNS 1424 1425 . . . 1426 1428 No no DT 1429 1440 significant significant JJ 1441 1452 differences difference NNS 1453 1460 between between IN 1461 1476 EBNA-2-positive ebna-2-positive JJ 1477 1480 and and CC 1481 1496 EBNA-2-negative ebna-2-negative JJ 1497 1504 nuclear nuclear JJ 1505 1513 extracts extract NNS 1514 1519 could could MD 1520 1522 be be VB 1523 1527 seen see VBN 1528 1530 in in IN 1531 1534 the the DT 1535 1538 gel gel NN 1539 1550 retardation retardation NN 1551 1556 assay assay NN 1557 1562 under under IN 1563 1573 conditions condition NNS 1574 1578 that that WDT 1579 1586 clearly clearly RB 1587 1593 showed show VBD 1594 1601 binding binding NN 1602 1604 of of IN 1605 1612 EBNA-2A EBNA-2A NNP 1613 1615 to to TO 1616 1619 the the DT 1620 1623 TP1 tp1 NN 1624 1632 promoter promoter NN 1632 1633 . . . 1634 1641 However however RB 1641 1642 , , , 1643 1651 analysis analysis NN 1652 1654 of of IN 1655 1662 sucrose sucrose NN 1663 1671 gradient gradient NN 1672 1681 fractions fraction NNS 1682 1684 in in IN 1685 1688 the the DT 1689 1692 gel gel NN 1693 1704 retardation retardation NN 1705 1710 assay assay NN 1711 1719 provided provide VBD 1720 1728 evidence evidence NN 1729 1733 that that IN 1734 1737 the the DT 1738 1741 LMP LMP NNP 1742 1758 promoter-binding promoter-binding JJ 1759 1767 proteins protein NNS 1768 1772 form form VBP 1773 1774 a a DT 1775 1782 complex complex NN 1783 1785 of of IN 1786 1792 higher high JJR 1793 1797 M(r) m(r) NN 1798 1800 in in IN 1801 1816 EBNA-2-positive ebna-2-positive JJ 1817 1821 cell cell NN 1822 1830 extracts extract NNS 1830 1831 . . . 1832 1837 These these DT 1838 1847 complexes complex NNS 1848 1852 were be VBD 1853 1862 destroyed destroy VBN 1863 1865 by by IN 1866 1875 detergent detergent NN 1875 1876 . . . 1877 1879 We we PRP 1880 1886 deduce deduce VBP 1887 1891 from from IN 1892 1897 these these DT 1898 1905 results result NNS 1906 1910 that that IN 1911 1926 EBNA-2-positive ebna-2-positive JJ 1927 1932 cells cell NNS 1933 1938 might might MD 1939 1945 indeed indeed RB 1946 1953 contain contain VB 1954 1962 specific specific JJ 1963 1972 complexes complex NNS 1973 1978 bound bind VBN 1979 1981 to to TO 1982 1985 the the DT 1986 1989 LMP LMP NNP 1990 1998 promoter promoter NN 1999 2004 which which WDT 2005 2008 are be VBP 2008 2009 , , , 2010 2017 however however RB 2017 2018 , , , 2019 2022 too too RB 2023 2029 labile labile JJ 2030 2032 to to TO 2033 2035 be be VB 2036 2044 detected detect VBN 2045 2047 in in IN 2048 2049 a a DT 2050 2058 standard standard JJ 2059 2062 gel gel NN 2063 2074 retardation retardation NN 2075 2080 assay assay NN 2080 2081 . . .