0 8 Positive positive JJ 9 19 regulators regulator NNS 20 22 of of IN 23 26 the the DT 27 43 lineage-specific lineage-specific JJ 44 57 transcription transcription NN 58 64 factor factor NN 65 71 GATA-1 gata-1 NN 72 74 in in IN 75 90 differentiating differentiate VBG 91 100 erythroid erythroid JJ 101 106 cells cell NNS 106 107 . . . 109 112 The the DT 113 117 zinc zinc NN 118 124 finger finger NN 125 138 transcription transcription NN 139 145 factor factor NN 146 152 GATA-1 gata-1 NN 153 155 is be VBZ 156 157 a a DT 158 163 major major JJ 164 173 regulator regulator NN 174 176 of of IN 177 181 gene gene NN 182 192 expression expression NN 193 195 in in IN 196 205 erythroid erythroid JJ 205 206 , , , 207 220 megakaryocyte megakaryocyte NN 220 221 , , , 222 225 and and CC 226 230 mast mast NN 231 235 cell cell NN 236 244 lineages lineage NNS 244 245 . . . 246 252 GATA-1 gata-1 NN 253 258 binds bind VBZ 259 261 to to TO 262 268 WGATAR WGATAR NNP 269 278 consensus consensus NN 279 285 motifs motif NNS 286 288 in in IN 289 292 the the DT 293 303 regulatory regulatory JJ 304 311 regions region NNS 312 314 of of IN 315 324 virtually virtually RB 325 328 all all DT 329 338 erythroid erythroid JJ 339 352 cell-specific cell-specific JJ 353 358 genes gene NNS 358 359 . . . 360 368 Analyses analysis NNS 369 373 with with IN 374 382 cultured culture VBN 383 388 cells cell NNS 389 392 and and CC 393 402 cell-free cell-free JJ 403 410 systems system NNS 411 415 have have VBP 416 424 provided provide VBN 425 431 strong strong JJ 432 440 evidence evidence NN 441 445 that that IN 446 452 GATA-1 gata-1 NN 453 455 is be VBZ 456 464 involved involve VBN 465 467 in in IN 468 475 control control NN 476 478 of of IN 479 485 globin globin NN 486 490 gene gene NN 491 501 expression expression NN 502 508 during during IN 509 518 erythroid erythroid JJ 519 534 differentiation differentiation NN 534 535 . . . 536 544 Targeted target VBN 545 556 mutagenesis mutagenesis NN 557 559 of of IN 560 563 the the DT 564 570 GATA-1 gata-1 NN 571 575 gene gene NN 576 578 in in IN 579 588 embryonic embryonic JJ 589 593 stem stem NN 594 599 cells cell NNS 600 603 has have VBZ 604 616 demonstrated demonstrate VBN 617 620 its its PRP$ 621 632 requirement requirement NN 633 635 in in IN 636 642 normal normal JJ 643 652 erythroid erythroid JJ 653 664 development development NN 664 665 . . . 666 675 Efficient efficient JJ 676 682 rescue rescue NN 683 685 of of IN 686 689 the the DT 690 696 defect defect NN 697 705 requires require VBZ 706 708 an an DT 709 715 intact intact JJ 716 720 GATA GATA NNP 721 728 element element NN 729 731 in in IN 732 735 the the DT 736 742 distal distal JJ 743 751 promoter promoter NN 751 752 , , , 753 763 suggesting suggest VBG 764 778 autoregulatory autoregulatory JJ 779 786 control control NN 787 789 of of IN 790 796 GATA-1 gata-1 NN 797 810 transcription transcription NN 810 811 . . . 812 814 To to TO 815 822 examine examine VB 823 830 whether whether IN 831 837 GATA-1 gata-1 NN 838 848 expression expression NN 849 857 involves involve VBZ 858 868 additional additional JJ 869 879 regulatory regulatory JJ 880 887 factors factor NNS 888 890 or or CC 891 893 is be VBZ 894 904 maintained maintain VBN 905 913 entirely entirely RB 914 916 by by IN 917 919 an an DT 920 934 autoregulatory autoregulatory JJ 935 939 loop loop NN 939 940 , , , 941 943 we we PRP 944 948 have have VBP 949 953 used use VBN 954 955 a a DT 956 965 transient transient JJ 966 978 heterokaryon heterokaryon NN 979 985 system system NN 986 988 to to TO 989 993 test test VB 994 997 the the DT 998 1005 ability ability NN 1006 1008 of of IN 1009 1018 erythroid erythroid JJ 1019 1026 factors factor NNS 1027 1029 to to TO 1030 1038 activate activate VB 1039 1042 the the DT 1043 1049 GATA-1 gata-1 NN 1050 1054 gene gene NN 1055 1057 in in IN 1058 1070 nonerythroid nonerythroid JJ 1071 1077 nuclei nucleus NNS 1077 1078 . . . 1079 1081 We we PRP 1082 1086 show show VBP 1087 1091 here here RB 1092 1096 that that IN 1097 1113 proerythroblasts proerythroblast NNS 1114 1117 and and CC 1118 1124 mature mature JJ 1125 1134 erythroid erythroid JJ 1135 1140 cells cell NNS 1141 1148 contain contain VBP 1149 1150 a a DT 1151 1161 diffusible diffusible JJ 1162 1170 activity activity NN 1171 1172 ( ( ( 1172 1175 TAG TAG NNP 1175 1176 ) ) ) 1177 1184 capable capable JJ 1185 1187 of of IN 1188 1203 transcriptional transcriptional JJ 1204 1214 activation activation NN 1215 1217 of of IN 1218 1224 GATA-1 gata-1 NN 1225 1228 and and CC 1229 1233 that that IN 1234 1238 this this DT 1239 1247 activity activity NN 1248 1257 decreases decrease VBZ 1258 1264 during during IN 1265 1268 the the DT 1269 1277 terminal terminal JJ 1278 1293 differentiation differentiation NN 1294 1296 of of IN 1297 1306 erythroid erythroid JJ 1307 1312 cells cell NNS 1312 1313 . . . 1314 1320 Nuclei Nucleus NNP 1321 1325 from from IN 1326 1333 GATA-1- gata-1- NN 1334 1340 mutant mutant JJ 1341 1350 embryonic embryonic JJ 1351 1355 stem stem NN 1356 1361 cells cell NNS 1362 1365 can can MD 1366 1371 still still RB 1372 1374 be be VB 1375 1387 reprogrammed reprogramme VBN 1388 1390 to to TO 1391 1398 express express VB 1399 1404 their their PRP$ 1405 1411 globin globin NN 1412 1417 genes gene NNS 1418 1420 in in IN 1421 1430 erythroid erythroid JJ 1431 1444 heterokaryons heterokaryon NNS 1444 1445 , , , 1446 1456 indicating indicate VBG 1457 1461 that that IN 1462 1464 de de FW 1465 1469 novo novo FW 1470 1479 induction induction NN 1480 1482 of of IN 1483 1489 GATA-1 gata-1 NN 1490 1492 is be VBZ 1493 1496 not not RB 1497 1505 required require VBN 1506 1509 for for IN 1510 1516 globin globin NN 1517 1521 gene gene NN 1522 1532 activation activation NN 1533 1542 following follow VBG 1543 1547 cell cell NN 1548 1554 fusion fusion NN 1554 1555 . . .