0 16 Ligand-dependent ligand-dependent JJ 17 27 repression repression NN 28 30 of of IN 31 34 the the DT 35 44 erythroid erythroid JJ 45 58 transcription transcription NN 59 65 factor factor NN 66 72 GATA-1 gata-1 NN 73 75 by by IN 76 79 the the DT 80 88 estrogen estrogen NN 89 97 receptor receptor NN 97 98 . . . 100 109 High-dose high-dose JJ 110 118 estrogen estrogen NN 119 133 administration administration NN 134 141 induces induce VBZ 142 148 anemia anemia NN 149 151 in in IN 152 159 mammals mammal NNS 159 160 . . . 161 163 In in IN 164 172 chickens chicken NNS 172 173 , , , 174 183 estrogens estrogen NNS 184 193 stimulate stimulate VBP 194 203 outgrowth outgrowth NN 204 206 of of IN 207 211 bone bone NN 212 226 marrow-derived marrow-derived JJ 227 236 erythroid erythroid JJ 237 247 progenitor progenitor NN 248 253 cells cell NNS 254 257 and and CC 258 263 delay delay VBP 264 269 their their PRP$ 270 280 maturation maturation NN 280 281 . . . 282 286 This this DT 287 292 delay delay NN 293 295 is be VBZ 296 306 associated associate VBN 307 311 with with IN 312 327 down-regulation down-regulation NN 328 330 of of IN 331 335 many many JJ 336 345 erythroid erythroid JJ 346 359 cell-specific cell-specific JJ 360 365 genes gene NNS 365 366 , , , 367 376 including include VBG 377 383 alpha- alpha- NN 384 387 and and CC 388 399 beta-globin beta-globin NN 399 400 , , , 401 405 band band NN 406 407 3 3 CD 407 408 , , , 409 413 band band NN 414 417 4.1 4.1 CD 417 418 , , , 419 422 and and CC 423 426 the the DT 427 436 erythroid erythroid JJ 437 450 cell-specific cell-specific JJ 451 458 histone histone NN 459 461 H5 h5 NN 461 462 . . . 463 465 We we PRP 466 470 show show VBP 471 475 here here RB 476 480 that that IN 481 490 estrogens estrogen NNS 491 495 also also RB 496 502 reduce reduce VBP 503 506 the the DT 507 513 number number NN 514 516 of of IN 517 526 erythroid erythroid JJ 527 537 progenitor progenitor NN 538 543 cells cell NNS 544 546 in in IN 547 554 primary primary JJ 555 560 human human JJ 561 565 bone bone NN 566 572 marrow marrow NN 573 581 cultures culture NNS 581 582 . . . 583 585 To to TO 586 593 address address VB 594 603 potential potential JJ 604 614 mechanisms mechanism NNS 615 617 by by IN 618 623 which which WDT 624 633 estrogens estrogen NNS 634 642 suppress suppress VBP 643 657 erythropoiesis erythropoiesis NN 657 658 , , , 659 661 we we PRP 662 666 have have VBP 667 675 examined examine VBN 676 681 their their PRP$ 682 689 effects effect NNS 690 692 on on IN 693 699 GATA-1 gata-1 NN 699 700 , , , 701 703 an an DT 704 713 erythroid erythroid JJ 714 727 transcription transcription NN 728 734 factor factor NN 735 739 that that WDT 740 752 participates participate VBZ 753 755 in in IN 756 759 the the DT 760 770 regulation regulation NN 771 773 of of IN 774 777 the the DT 778 786 majority majority NN 787 789 of of IN 790 799 erythroid erythroid JJ 800 813 cell-specific cell-specific JJ 814 819 genes gene NNS 820 823 and and CC 824 826 is be VBZ 827 836 necessary necessary JJ 837 840 for for IN 841 845 full full JJ 846 856 maturation maturation NN 857 859 of of IN 860 872 erythrocytes erythrocyte NNS 872 873 . . . 874 876 We we PRP 877 888 demonstrate demonstrate VBP 889 893 that that IN 894 897 the the DT 898 913 transcriptional transcriptional JJ 914 922 activity activity NN 923 925 of of IN 926 932 GATA-1 gata-1 NN 933 935 is be VBZ 936 944 strongly strongly RB 945 954 repressed repress VBN 955 957 by by IN 958 961 the the DT 962 970 estrogen estrogen NN 971 979 receptor receptor NN 980 981 ( ( ( 981 983 ER ER NNP 983 984 ) ) ) 985 987 in in IN 988 989 a a DT 990 1006 ligand-dependent ligand-dependent JJ 1007 1013 manner manner NN 1014 1017 and and CC 1018 1022 that that IN 1023 1027 this this DT 1028 1038 repression repression NN 1039 1041 is be VBZ 1042 1052 reversible reversible JJ 1053 1055 in in IN 1056 1059 the the DT 1060 1068 presence presence NN 1069 1071 of of IN 1072 1090 4-hydroxytamoxifen 4-hydroxytamoxifen NN 1090 1091 . . . 1092 1103 ER-mediated er-mediated JJ 1104 1114 repression repression NN 1115 1117 of of IN 1118 1124 GATA-1 gata-1 NN 1125 1133 activity activity NN 1134 1140 occurs occur VBZ 1141 1143 on on IN 1144 1146 an an DT 1147 1157 artificial artificial JJ 1158 1166 promoter promoter NN 1167 1177 containing contain VBG 1178 1179 a a DT 1180 1186 single single JJ 1187 1199 GATA-binding gata-binding JJ 1200 1204 site site NN 1204 1205 , , , 1206 1208 as as RB 1209 1213 well well RB 1214 1216 as as IN 1217 1219 in in IN 1220 1223 the the DT 1224 1231 context context NN 1232 1234 of of IN 1235 1237 an an DT 1238 1244 intact intact JJ 1245 1253 promoter promoter NN 1254 1259 which which WDT 1260 1262 is be VBZ 1263 1271 normally normally RB 1272 1281 regulated regulate VBN 1282 1284 by by IN 1285 1291 GATA-1 gata-1 NN 1291 1292 . . . 1293 1299 GATA-1 gata-1 NN 1300 1303 and and CC 1304 1306 ER ER NNP 1307 1311 bind bind VBP 1312 1314 to to TO 1315 1319 each each DT 1320 1325 other other JJ 1326 1328 in in FW 1329 1334 vitro vitro FW 1335 1337 in in IN 1338 1341 the the DT 1342 1349 absence absence NN 1350 1352 of of IN 1353 1356 DNA DNA NNP 1356 1357 . . . 1358 1360 In in IN 1361 1382 coimmunoprecipitation coimmunoprecipitation NN 1383 1394 experiments experiment NNS 1395 1400 using use VBG 1401 1412 transfected transfecte VBN 1413 1416 COS cos NN 1417 1422 cells cell NNS 1422 1423 , , , 1424 1430 GATA-1 gata-1 NN 1431 1434 and and CC 1435 1437 ER er NN 1438 1447 associate associate VBP 1448 1450 in in IN 1451 1452 a a DT 1453 1469 ligand-dependent ligand-dependent JJ 1470 1476 manner manner NN 1476 1477 . . . 1478 1485 Mapping map VBG 1486 1497 experiments experiment NNS 1498 1506 indicate indicate VBP 1507 1511 that that IN 1512 1518 GATA-1 gata-1 NN 1519 1522 and and CC 1523 1526 the the DT 1527 1529 ER er NN 1530 1534 form form NN 1535 1537 at at IN 1538 1543 least least JJS 1544 1547 two two CD 1548 1556 contacts contact NNS 1556 1557 , , , 1558 1563 which which WDT 1564 1571 involve involve VBP 1572 1575 the the DT 1576 1582 finger finger NN 1583 1589 region region NN 1590 1593 and and CC 1594 1597 the the DT 1598 1608 N-terminal n-terminal JJ 1609 1619 activation activation NN 1620 1626 domain domain NN 1627 1629 of of IN 1630 1636 GATA-1 gata-1 NN 1636 1637 . . . 1638 1640 We we PRP 1641 1650 speculate speculate VBP 1651 1655 that that IN 1656 1665 estrogens estrogen NNS 1666 1671 exert exert VBP 1672 1679 effects effect NNS 1680 1682 on on IN 1683 1697 erythropoiesis erythropoiesis NN 1698 1700 by by IN 1701 1711 modulating modulate VBG 1712 1718 GATA-1 gata-1 NN 1719 1727 activity activity NN 1728 1735 through through IN 1736 1751 protein-protein protein-protein JJ 1752 1763 interaction interaction NN 1764 1768 with with IN 1769 1772 the the DT 1773 1775 ER er NN 1775 1776 . . . 1777 1778 ( ( ( 1778 1786 ABSTRACT abstract NN 1787 1796 TRUNCATED truncated VBN 1797 1799 AT at IN 1800 1803 250 250 CD 1804 1809 WORDS words NNS 1809 1810 ) ) )