0 6 Direct direct JJ 7 18 interaction interaction NN 19 21 of of IN 22 35 hematopoietic hematopoietic JJ 36 49 transcription transcription NN 50 57 factors factor NNS 58 62 PU.1 pu.1 NN 63 66 and and CC 67 73 GATA-1 gata-1 NN 73 74 : : : 75 85 functional functional JJ 86 96 antagonism antagonism NN 97 99 in in IN 100 109 erythroid erythroid JJ 110 115 cells cell NNS 115 116 . . . 118 127 Malignant malignant JJ 128 142 transformation transformation NN 143 150 usually usually RB 151 159 inhibits inhibit VBZ 160 168 terminal terminal JJ 169 173 cell cell NN 174 189 differentiation differentiation NN 190 193 but but CC 194 197 the the DT 198 205 precise precise JJ 206 216 mechanisms mechanism NNS 217 225 involved involve VBN 226 229 are be VBP 230 233 not not RB 234 244 understood understand VBN 244 245 . . . 246 250 PU.1 PU.1 NNP 251 253 is be VBZ 254 255 a a DT 256 278 hematopoietic-specific hematopoietic-specific JJ 279 282 Ets Ets NNP 283 289 family family NN 290 303 transcription transcription NN 304 310 factor factor NN 311 315 that that WDT 316 318 is be VBZ 319 327 required require VBN 328 331 for for IN 332 343 development development NN 344 346 of of IN 347 351 some some DT 352 360 lymphoid lymphoid JJ 361 364 and and CC 365 372 myeloid myeloid JJ 373 381 lineages lineage NNS 381 382 . . . 383 387 PU.1 PU.1 NNP 388 391 can can MD 392 396 also also RB 397 400 act act VB 401 403 as as IN 404 406 an an DT 407 418 oncoprotein oncoprotein NN 419 421 as as IN 422 432 activation activation NN 433 435 of of IN 436 439 its its PRP$ 440 450 expression expression NN 451 453 in in IN 454 463 erythroid erythroid JJ 464 474 precursors precursor NNS 475 477 by by IN 478 486 proviral proviral JJ 487 496 insertion insertion NN 497 499 or or CC 500 512 transgenesis transgenesis NN 513 519 causes cause VBZ 520 536 erythroleukemias erythroleukemia NNS 537 539 in in IN 540 544 mice mouse NNS 544 545 . . . 546 557 Restoration Restoration NNP 558 560 of of IN 561 569 terminal terminal JJ 570 585 differentiation differentiation NN 586 588 in in IN 589 592 the the DT 593 598 mouse mouse NN 599 614 erythroleukemia erythroleukemia NN 615 616 ( ( ( 616 619 MEL MEL NNP 619 620 ) ) ) 621 626 cells cell NNS 627 635 requires require VBZ 636 637 a a DT 638 645 decline decline NN 646 648 in in IN 649 652 the the DT 653 658 level level NN 659 661 of of IN 662 666 PU.1 PU.1 NNP 666 667 , , , 668 678 indicating indicate VBG 679 683 that that IN 684 688 PU.1 pu.1 NN 689 692 can can MD 693 698 block block VB 699 708 erythroid erythroid JJ 709 724 differentiation differentiation NN 724 725 . . . 726 730 Here here RB 731 733 we we PRP 734 745 investigate investigate VBP 746 749 the the DT 750 759 mechanism mechanism NN 760 762 by by IN 763 768 which which WDT 769 773 PU.1 PU.1 NNP 774 784 interferes interfere VBZ 785 789 with with IN 790 799 erythroid erythroid JJ 800 815 differentiation differentiation NN 815 816 . . . 817 819 We we PRP 820 824 find find VBP 825 829 that that IN 830 834 PU.1 pu.1 NN 835 844 interacts interact VBZ 845 853 directly directly RB 854 858 with with IN 859 865 GATA-1 gata-1 NN 865 866 , , , 867 868 a a DT 869 873 zinc zinc NN 874 880 finger finger NN 881 894 transcription transcription NN 895 901 factor factor NN 902 910 required require VBN 911 914 for for IN 915 924 erythroid erythroid JJ 925 940 differentiation differentiation NN 940 941 . . . 942 953 Interaction Interaction NNP 954 961 between between IN 962 966 PU.1 PU.1 NNP 967 970 and and CC 971 977 GATA-1 GATA-1 NNP 978 986 requires require VBZ 987 993 intact intact JJ 994 1005 DNA-binding dna-binding JJ 1006 1013 domains domain NNS 1014 1016 in in IN 1017 1021 both both DT 1022 1030 proteins protein NNS 1030 1031 . . . 1032 1036 PU.1 PU.1 NNP 1037 1046 represses repress VBZ 1047 1062 GATA-1-mediated gata-1-mediated JJ 1063 1078 transcriptional transcriptional JJ 1079 1089 activation activation NN 1089 1090 . . . 1091 1095 Both both CC 1096 1099 the the DT 1100 1103 DNA dna NN 1104 1111 binding binding NN 1112 1115 and and CC 1116 1131 transactivation transactivation NN 1132 1139 domains domain NNS 1140 1142 of of IN 1143 1147 PU.1 PU.1 NNP 1148 1151 are be VBP 1152 1160 required require VBN 1161 1164 for for IN 1165 1175 repression repression NN 1176 1179 and and CC 1180 1184 both both DT 1185 1192 domains domain NNS 1193 1196 are be VBP 1197 1201 also also RB 1202 1208 needed need VBN 1209 1211 to to TO 1212 1217 block block VB 1218 1226 terminal terminal JJ 1227 1242 differentiation differentiation NN 1243 1245 in in IN 1246 1249 MEL MEL NNP 1250 1255 cells cell NNS 1255 1256 . . . 1257 1259 We we PRP 1260 1264 also also RB 1265 1269 show show VBP 1270 1274 that that IN 1275 1282 ectopic ectopic JJ 1283 1293 expression expression NN 1294 1296 of of IN 1297 1301 PU.1 pu.1 NN 1302 1304 in in IN 1305 1312 Xenopus Xenopus NNP 1313 1320 embryos embryo NNS 1321 1323 is be VBZ 1324 1334 sufficient sufficient JJ 1335 1337 to to TO 1338 1343 block block VB 1344 1358 erythropoiesis erythropoiesis NN 1359 1365 during during IN 1366 1372 normal normal JJ 1373 1384 development development NN 1384 1385 . . . 1386 1397 Furthermore furthermore RB 1397 1398 , , , 1399 1411 introduction introduction NN 1412 1414 of of IN 1415 1424 exogenous exogenous JJ 1425 1431 GATA-1 gata-1 NN 1432 1434 in in IN 1435 1439 both both DT 1440 1443 MEL MEL NNP 1444 1449 cells cell NNS 1450 1453 and and CC 1454 1461 Xenopus xenopus NN 1462 1469 embryos embryo NNS 1470 1473 and and CC 1474 1482 explants explant NNS 1483 1491 relieves relieve VBZ 1492 1495 the the DT 1496 1501 block block NN 1502 1504 to to TO 1505 1514 erythroid erythroid JJ 1515 1530 differentiation differentiation NN 1531 1538 imposed impose VBN 1539 1541 by by IN 1542 1546 PU.1 PU.1 NNP 1546 1547 . . . 1548 1551 Our our PRP$ 1552 1559 results result NNS 1560 1568 indicate indicate VBP 1569 1573 that that IN 1574 1577 the the DT 1578 1591 stoichiometry stoichiometry NN 1592 1594 of of IN 1595 1603 directly directly RB 1604 1615 interacting interact VBG 1616 1619 but but CC 1620 1628 opposing oppose VBG 1629 1642 transcription transcription NN 1643 1650 factors factor NNS 1651 1654 may may MD 1655 1657 be be VB 1658 1659 a a DT 1660 1667 crucial crucial JJ 1668 1679 determinant determinant NN 1680 1689 governing govern VBG 1690 1699 processes process NNS 1700 1702 of of IN 1703 1709 normal normal JJ 1710 1725 differentiation differentiation NN 1726 1729 and and CC 1730 1739 malignant malignant JJ 1740 1754 transformation transformation NN 1754 1755 . . .