0 8 Retinoid Retinoid NNP 9 10 X X NNP 11 19 receptor receptor NN 20 23 and and CC 24 39 c-cerbA/thyroid c-cerba/thyroid NN 40 47 hormone hormone NN 48 56 receptor receptor NN 57 65 regulate regulate VBP 66 75 erythroid erythroid JJ 76 80 cell cell NN 81 87 growth growth NN 88 91 and and CC 92 107 differentiation differentiation NN 107 108 . . . 110 117 Nuclear nuclear JJ 118 127 receptors receptor NNS 128 131 are be VBP 132 141 important important JJ 142 152 regulators regulator NNS 153 155 of of IN 156 165 erythroid erythroid JJ 166 170 cell cell NN 171 182 development development NN 182 183 . . . 184 188 Here here RB 189 191 we we PRP 192 204 investigated investigate VBD 205 208 the the DT 209 215 impact impact NN 216 218 of of IN 219 227 retinoid retinoid NN 228 229 X X NNP 230 238 receptor receptor NN 239 240 ( ( ( 240 243 RXR RXR NNP 243 244 ) ) ) 244 245 , , , 246 254 retinoic retinoic JJ 255 259 acid acid NN 260 268 receptor receptor NN 269 270 ( ( ( 270 273 RAR RAR NNP 273 274 ) ) ) 274 275 , , , 276 279 and and CC 280 282 of of IN 283 286 the the DT 287 301 c-erbA/thyroid c-erba/thyroid NN 302 309 hormone hormone NN 310 311 ( ( ( 311 313 T3 T3 NNP 313 314 ) ) ) 315 323 receptor receptor NN 324 325 ( ( ( 325 334 c-erbA/TR c-erbA/TR NNP 334 335 ) ) ) 336 338 on on IN 339 345 growth growth NN 346 349 and and CC 350 365 differentiation differentiation NN 366 368 of of IN 369 378 erythroid erythroid JJ 379 384 cells cell NNS 385 390 using use VBG 391 393 an an DT 394 396 in in FW 397 402 vitro vitro FW 403 410 culture culture NN 411 417 system system NN 418 420 of of IN 421 425 stem stem NN 426 430 cell cell NN 431 447 factor-dependent factor-dependent JJ 448 457 erythroid erythroid JJ 458 469 progenitors progenitor NNS 469 470 . . . 471 474 RXR RXR NNP 474 475 , , , 476 479 RAR RAR NNP 479 480 , , , 481 484 and and CC 485 503 c-erbA/TR-specific c-erba/tr-specific JJ 504 511 ligands ligand NNS 512 516 were be VBD 517 522 found find VBN 523 525 to to TO 526 532 induce induce VB 533 551 erythroid-specific erythroid-specific JJ 552 556 gene gene NN 557 567 expression expression NN 568 571 and and CC 572 574 to to TO 575 585 accelerate accelerate VB 586 595 erythroid erythroid JJ 596 611 differentiation differentiation NN 612 614 in in IN 615 622 culture culture NN 622 623 , , , 624 628 with with IN 629 631 T3 t3 NN 632 637 being be VBG 638 642 most most RBS 643 652 effective effective JJ 652 653 . . . 654 665 Furthermore furthermore RB 665 666 , , , 667 672 while while IN 673 689 ligand-activated ligand-activated JJ 690 699 c-erbA/TR c-erbA/TR NNP 700 711 accelerated accelerate VBD 712 727 differentiation differentiation NN 727 728 , , , 729 739 unliganded unliganded JJ 740 749 c-erbA/TR c-erbA/TR NNP 750 761 effectively effectively RB 762 769 blocked block VBD 770 785 differentiation differentiation NN 786 789 and and CC 790 799 supported support VBD 800 809 sustained sustained JJ 810 820 progenitor progenitor NN 821 827 growth growth NN 828 830 in in IN 831 838 culture culture NN 838 839 . . . 840 844 Thus thus RB 844 845 , , , 846 855 c-erbA/TR c-erbA/TR NNP 856 863 appears appear VBZ 864 866 to to TO 867 870 act act VB 871 873 as as IN 874 875 a a DT 876 882 binary binary JJ 883 889 switch switch NN 890 899 affecting affect VBG 900 909 erythroid erythroid JJ 910 914 cell cell NN 915 919 fate fate NN 919 920 : : : 921 931 unliganded unliganded JJ 932 941 c-erbA/TR c-erbA/TR NNP 942 950 supports support VBZ 951 957 growth growth NN 958 963 while while IN 964 980 ligand-activated ligand-activated JJ 981 990 c-erbA/TR c-erbA/TR NNP 991 998 induces induce VBZ 999 1014 differentiation differentiation NN 1014 1015 . . . 1016 1028 Additionally additionally RB 1028 1029 , , , 1030 1032 to to TO 1033 1042 determine determine VB 1043 1046 the the DT 1047 1053 impact impact NN 1054 1056 of of IN 1057 1060 RXR rxr NN 1061 1064 for for IN 1065 1074 erythroid erythroid JJ 1075 1079 cell cell NN 1080 1091 development development NN 1091 1092 , , , 1093 1101 dominant dominant JJ 1102 1113 interfering interfere VBG 1114 1120 mutant mutant JJ 1121 1125 RXRs rxr NNS 1125 1126 , , , 1127 1134 lacking lack VBG 1135 1138 the the DT 1139 1154 transcriptional transcriptional JJ 1155 1164 activator activator NN 1165 1174 functions function NNS 1175 1179 AF-1 af-1 NN 1180 1183 and and CC 1184 1188 AF-2 af-2 NN 1188 1189 , , , 1190 1192 or or CC 1193 1197 AF-2 af-2 NN 1198 1202 only only RB 1202 1203 , , , 1204 1206 or or CC 1207 1210 the the DT 1211 1217 entire entire JJ 1218 1229 DNA-binding dna-binding JJ 1230 1236 domain domain NN 1236 1237 , , , 1238 1242 were be VBD 1243 1253 introduced introduce VBN 1254 1258 into into IN 1259 1268 erythroid erythroid JJ 1269 1279 progenitor progenitor NN 1280 1285 cells cell NNS 1286 1289 via via IN 1290 1301 recombinant recombinant JJ 1302 1312 retrovirus retrovirus NN 1313 1320 vectors vector NNS 1321 1324 and and CC 1325 1333 analyzed analyze VBN 1334 1337 for for IN 1338 1350 RXR-specific rxr-specific JJ 1351 1358 effects effect NNS 1358 1359 . . . 1360 1362 It it PRP 1363 1366 was be VBD 1367 1372 found find VBN 1373 1377 that that IN 1378 1388 expression expression NN 1389 1391 of of IN 1392 1401 wild-type wild-type JJ 1402 1405 RXR rxr NN 1406 1409 and and CC 1410 1412 of of IN 1413 1416 the the DT 1417 1420 RXR rxr NN 1421 1428 mutants mutant NNS 1429 1435 devoid devoid JJ 1436 1438 of of IN 1439 1443 AF-1 AF-1 NNP 1444 1450 and/or and/or CC 1451 1455 AF-2 AF-2 NNP 1456 1465 supported support VBD 1466 1467 a a DT 1468 1477 transient transient JJ 1478 1487 outgrowth outgrowth NN 1488 1490 of of IN 1491 1500 erythroid erythroid JJ 1501 1506 cells cell NNS 1506 1507 . . . 1508 1510 In in IN 1511 1517 marked marked JJ 1518 1526 contrast contrast NN 1526 1527 , , , 1528 1538 expression expression NN 1539 1541 of of IN 1542 1545 the the DT 1546 1554 dominant dominant JJ 1555 1566 interfering interfere VBG 1567 1583 deltaDNA-binding deltadna-binding JJ 1584 1590 domain domain NN 1591 1594 RXR rxr NN 1594 1595 , , , 1596 1606 containing contain VBG 1607 1608 a a DT 1609 1617 deletion deletion NN 1618 1620 of of IN 1621 1624 the the DT 1625 1631 entire entire JJ 1632 1643 DNA-binding dna-binding JJ 1644 1650 domain domain NN 1650 1651 , , , 1652 1655 was be VBD 1656 1668 incompatible incompatible JJ 1669 1673 with with IN 1674 1683 erythroid erythroid JJ 1684 1688 cell cell NN 1689 1695 growth growth NN 1696 1698 in in FW 1699 1704 vitro vitro FW 1704 1705 , , , 1706 1716 suggesting suggest VBG 1717 1718 a a DT 1719 1726 pivotal pivotal JJ 1727 1731 role role NN 1732 1734 of of IN 1735 1738 RXR rxr NN 1739 1742 for for IN 1743 1752 erythroid erythroid JJ 1753 1757 cell cell NN 1758 1769 development development NN 1769 1770 . . .