0 15 Transcriptional transcriptional JJ 16 24 activity activity NN 25 27 of of IN 28 32 core core NN 33 40 binding binding NN 41 53 factor-alpha factor-alpha NN 54 55 ( ( ( 55 59 AML1 AML1 NNP 59 60 ) ) ) 61 64 and and CC 65 69 beta beta NN 70 78 subunits subunit NNS 79 81 on on IN 82 88 murine murine JJ 89 97 leukemia leukemia NN 98 103 virus virus NN 104 112 enhancer enhancer NN 113 118 cores core NNS 118 119 . . . 121 125 Core Core NNP 126 133 binding binding NN 134 140 factor factor NN 141 142 ( ( ( 142 145 CBF CBF NNP 145 146 ) ) ) 146 147 , , , 148 152 also also RB 153 158 known know VBN 159 161 as as IN 162 174 polyomavirus polyomavirus NN 175 191 enhancer-binding enhancer-binding JJ 192 199 protein protein NN 200 201 2 2 CD 202 205 and and CC 206 209 SL3 sl3 NN 210 218 enhancer enhancer NN 219 225 factor factor NN 226 227 1 1 CD 227 228 , , , 229 231 is be VBZ 232 233 a a DT 234 243 mammalian mammalian JJ 244 257 transcription transcription NN 258 264 factor factor NN 265 269 that that WDT 270 275 binds bind VBZ 276 278 to to TO 279 281 an an DT 282 289 element element NN 290 296 termed term VBN 297 300 the the DT 301 305 core core NN 306 312 within within IN 313 316 the the DT 317 326 enhancers enhancer NNS 327 329 of of IN 330 333 the the DT 334 340 murine murine JJ 341 349 leukemia leukemia NN 350 355 virus virus NN 356 362 family family NN 363 365 of of IN 366 378 retroviruses retrovirus NNS 378 379 . . . 380 383 The the DT 384 388 core core NN 389 397 elements element NNS 398 400 of of IN 401 404 the the DT 405 408 SL3 sl3 NN 409 414 virus virus NN 415 418 are be VBP 419 428 important important JJ 429 436 genetic genetic JJ 437 449 determinants determinant NNS 450 452 of of IN 453 456 the the DT 457 464 ability ability NN 465 467 of of IN 468 472 this this DT 473 478 virus virus NN 479 481 to to TO 482 488 induce induce VB 489 495 T-cell t-cell NN 496 505 lymphomas lymphoma NNS 506 509 and and CC 510 513 the the DT 514 529 transcriptional transcriptional JJ 530 538 activity activity NN 539 541 of of IN 542 545 the the DT 546 551 viral viral JJ 552 556 long long JJ 557 565 terminal terminal JJ 566 572 repeat repeat NN 573 575 in in IN 576 577 T t NN 578 589 lymphocytes lymphocyte NNS 589 590 . . . 591 594 CBF CBF NNP 595 603 consists consist VBZ 604 606 of of IN 607 610 two two CD 611 619 subunits subunit NNS 619 620 , , , 621 622 a a DT 623 626 DNA DNA NNP 627 634 binding binding NN 635 642 subunit subunit NN 642 643 , , , 644 647 CBF CBF NNP 648 653 alpha alpha NN 653 654 , , , 655 658 and and CC 659 660 a a DT 661 667 second second JJ 668 675 subunit subunit NN 675 676 , , , 677 680 CBF CBF NNP 681 685 beta beta NN 685 686 , , , 687 691 that that WDT 692 702 stimulates stimulate VBZ 703 706 the the DT 707 710 DNA dna NN 711 718 binding binding NN 719 727 activity activity NN 728 730 of of IN 731 734 CBF CBF NNP 735 740 alpha alpha NN 740 741 . . . 742 745 One one CD 746 748 of of IN 749 752 the the DT 753 758 genes gene NNS 759 763 that that WDT 764 771 encodes encode VBZ 772 773 a a DT 774 777 CBF CBF NNP 778 783 alpha alpha NN 784 791 subunit subunit NN 792 794 is be VBZ 795 799 AML1 aml1 NN 799 800 , , , 801 805 also also RB 806 812 called call VBN 813 816 Cbf Cbf NNP 817 822 alpha alpha NN 823 824 2 2 CD 824 825 . . . 826 830 This this DT 831 836 locus locus NN 837 839 is be VBZ 840 850 rearranged rearrange VBN 851 853 by by IN 854 865 chromosomal chromosomal JJ 866 880 translocations translocation NNS 881 883 in in IN 884 889 human human JJ 890 908 myeloproliferative myeloproliferative JJ 909 918 disorders disorder NNS 919 922 and and CC 923 932 leukemias leukemia NNS 932 933 . . . 934 936 An an DT 937 948 exogenously exogenously RB 949 958 expressed express VBN 959 962 Cbf Cbf NNP 963 968 alpha alpha NN 969 978 2-encoded 2-encoded JJ 979 986 subunit subunit NN 987 988 ( ( ( 988 991 CBF CBF NNP 992 997 alpha alpha NN 998 1003 2-451 2-451 CD 1003 1004 ) ) ) 1005 1015 stimulated stimulate VBD 1016 1029 transcription transcription NN 1030 1034 from from IN 1035 1038 the the DT 1039 1042 SL3 sl3 NN 1043 1051 enhancer enhancer NN 1052 1054 in in IN 1055 1058 P19 P19 NNP 1059 1062 and and CC 1063 1067 HeLa HeLa NNP 1068 1073 cells cell NNS 1073 1074 . . . 1075 1083 Activity activity NN 1084 1087 was be VBD 1088 1096 mediated mediate VBN 1097 1104 through through IN 1105 1108 the the DT 1109 1113 core core NN 1114 1122 elements element NNS 1122 1123 . . . 1124 1129 Three three CD 1130 1139 different different JJ 1140 1148 isoforms isoform NNS 1149 1151 of of IN 1152 1155 CBF CBF NNP 1156 1160 beta beta NN 1161 1165 were be VBD 1166 1170 also also RB 1171 1177 tested test VBN 1178 1181 for for IN 1182 1197 transcriptional transcriptional JJ 1198 1206 activity activity NN 1207 1209 on on IN 1210 1213 the the DT 1214 1217 SL3 sl3 NN 1218 1226 enhancer enhancer NN 1226 1227 . . . 1228 1231 The the DT 1232 1239 longest long JJS 1240 1244 form form NN 1244 1245 , , , 1246 1249 CBF CBF NNP 1250 1258 beta-187 beta-187 NN 1258 1259 , , , 1260 1269 increased increase VBD 1270 1273 the the DT 1274 1289 transcriptional transcriptional JJ 1290 1301 stimulation stimulation NN 1302 1304 by by IN 1305 1308 CBF CBF NNP 1309 1314 alpha alpha NN 1315 1320 2-451 2-451 CD 1321 1328 twofold twofold RB 1329 1331 in in IN 1332 1336 HeLa HeLa NNP 1337 1342 cells cell NNS 1342 1343 , , , 1344 1352 although although IN 1353 1355 it it PRP 1356 1359 had have VBD 1360 1362 no no DT 1363 1369 effect effect NN 1370 1372 in in IN 1373 1376 P19 p19 NN 1377 1382 cells cell NNS 1382 1383 . . . 1384 1399 Transcriptional transcriptional JJ 1400 1410 activation activation NN 1411 1413 by by IN 1414 1417 CBF CBF NNP 1418 1422 beta beta NN 1423 1431 required require VBD 1432 1439 binding binding NN 1440 1442 to to TO 1443 1446 the the DT 1447 1450 CBF CBF NNP 1451 1456 alpha alpha NN 1457 1464 subunit subunit NN 1464 1465 , , , 1466 1468 as as IN 1469 1470 a a DT 1471 1475 form form NN 1476 1478 of of IN 1479 1482 CBF CBF NNP 1483 1487 beta beta NN 1488 1492 that that WDT 1493 1499 lacked lack VBD 1500 1507 binding binding NN 1508 1515 ability ability NN 1515 1516 , , , 1517 1520 CBF CBF NNP 1521 1529 beta-148 beta-148 NN 1529 1530 , , , 1531 1537 failed fail VBD 1538 1540 to to TO 1541 1549 increase increase VB 1550 1558 activity activity NN 1558 1559 . . . 1560 1565 These these DT 1566 1573 results result NNS 1574 1583 indicated indicate VBD 1584 1588 that that IN 1589 1591 at at IN 1592 1597 least least JJS 1598 1600 in in IN 1601 1608 certain certain JJ 1609 1613 cell cell NN 1614 1619 types type NNS 1619 1620 , , , 1621 1624 the the DT 1625 1632 maximum maximum NN 1633 1641 activity activity NN 1642 1644 of of IN 1645 1648 CBF CBF NNP 1649 1657 required require VBD 1658 1662 both both DT 1663 1671 subunits subunit NNS 1671 1672 . . . 1673 1677 They they PRP 1678 1682 also also RB 1683 1691 provided provide VBD 1692 1699 support support NN 1700 1703 for for IN 1704 1707 the the DT 1708 1718 hypothesis hypothesis NN 1719 1723 that that IN 1724 1727 CBF CBF NNP 1728 1730 is be VBZ 1731 1732 a a DT 1733 1739 factor factor NN 1740 1742 in in IN 1743 1744 T t NN 1745 1756 lymphocytes lymphocyte NNS 1757 1761 that that WDT 1762 1764 is be VBZ 1765 1776 responsible responsible JJ 1777 1780 for for IN 1781 1792 recognition recognition NN 1793 1795 of of IN 1796 1799 the the DT 1800 1803 SL3 sl3 NN 1804 1809 cores core NNS 1809 1810 . . . 1811 1813 We we PRP 1814 1818 also also RB 1819 1827 examined examine VBD 1828 1835 whether whether IN 1836 1839 CBF CBF NNP 1840 1845 could could MD 1846 1857 distinguish distinguish VB 1858 1859 a a DT 1860 1864 1-bp 1-bp JJ 1865 1875 difference difference NN 1876 1883 between between IN 1884 1887 the the DT 1888 1896 enhancer enhancer NN 1897 1901 core core NN 1902 1904 of of IN 1905 1908 SL3 SL3 NNP 1909 1912 and and CC 1913 1916 the the DT 1917 1921 core core NN 1922 1924 of of IN 1925 1928 the the DT 1929 1944 nonleukemogenic nonleukemogenic JJ 1945 1950 virus virus NN 1950 1951 , , , 1952 1955 Akv Akv NNP 1955 1956 . . . 1957 1961 This this DT 1962 1972 difference difference NN 1973 1981 strongly strongly RB 1982 1989 affects affect VBZ 1990 2003 transcription transcription NN 2004 2006 in in IN 2007 2008 T t NN 2009 2014 cells cell NNS 2015 2018 and and CC 2019 2034 leukemogenicity leukemogenicity NN 2035 2037 of of IN 2038 2041 SL3 SL3 NNP 2041 2042 . . . 2043 2050 However however RB 2050 2051 , , , 2052 2054 no no DT 2055 2066 combination combination NN 2067 2069 of of IN 2070 2073 CBF CBF NNP 2074 2079 alpha alpha NN 2080 2083 and and CC 2084 2087 CBF cbf NN 2088 2092 beta beta NN 2093 2101 subunits subunit NNS 2102 2106 that that WDT 2107 2109 we we PRP 2110 2116 tested test VBD 2117 2120 was be VBD 2121 2125 able able JJ 2126 2128 to to TO 2129 2140 distinguish distinguish VB 2141 2144 the the DT 2145 2149 1-bp 1-bp JJ 2150 2160 difference difference NN 2161 2163 in in IN 2164 2177 transcription transcription NN 2178 2184 assays assay NNS 2184 2185 . . . 2186 2190 Thus thus RB 2190 2191 , , , 2192 2193 a a DT 2194 2202 complete complete JJ 2203 2216 understanding understanding NN 2217 2219 of of IN 2220 2223 how how WRB 2224 2225 T t NN 2226 2231 cells cell NNS 2232 2241 recognize recognize VBP 2242 2245 the the DT 2246 2249 SL3 sl3 NN 2250 2254 core core NN 2255 2262 remains remain VBZ 2263 2265 to to TO 2266 2268 be be VB 2269 2279 elucidated elucidate VBN 2279 2280 . . .