0 10 Regulation regulation NN 11 13 of of IN 14 27 transcription transcription NN 28 30 of of IN 31 34 the the DT 35 40 human human JJ 41 55 erythropoietin erythropoietin NN 56 64 receptor receptor NN 65 69 gene gene NN 70 72 by by IN 73 81 proteins protein NNS 82 89 binding bind VBG 90 92 to to TO 93 99 GATA-1 gata-1 NN 100 103 and and CC 104 107 Sp1 sp1 NN 108 114 motifs motif NNS 114 115 . . . 117 131 Erythropoietin erythropoietin NN 132 133 ( ( ( 133 136 Epo Epo NNP 136 137 ) ) ) 137 138 , , , 139 142 the the DT 143 150 primary primary JJ 151 160 regulator regulator NN 161 163 of of IN 164 167 the the DT 168 178 production production NN 179 181 of of IN 182 191 erythroid erythroid JJ 192 197 cells cell NNS 197 198 , , , 199 203 acts act VBZ 204 206 by by IN 207 214 binding bind VBG 215 217 to to TO 218 219 a a DT 220 224 cell cell NN 225 232 surface surface NN 233 241 receptor receptor NN 242 243 ( ( ( 243 247 EpoR EpoR NNP 247 248 ) ) ) 249 251 on on IN 252 261 erythroid erythroid JJ 262 273 progenitors progenitor NNS 273 274 . . . 275 277 We we PRP 278 282 used use VBD 283 291 deletion deletion NN 292 300 analysis analysis NN 301 304 and and CC 305 317 transfection transfection NN 318 324 assays assay NNS 325 329 with with IN 330 338 reporter reporter NN 339 343 gene gene NN 344 354 constructs construct NNS 355 357 to to TO 358 365 examine examine VB 366 369 the the DT 370 383 transcription transcription NN 384 391 control control NN 392 400 elements element NNS 401 403 in in IN 404 407 the the DT 408 409 5 5 CD 409 410 ’ ' SYM 411 419 flanking flanking NN 420 426 region region NN 427 429 of of IN 430 433 the the DT 434 439 human human JJ 440 444 EpoR epor NN 445 449 gene gene NN 449 450 . . . 451 453 In in IN 454 463 erythroid erythroid JJ 464 469 cells cell NNS 470 474 most most JJS 475 477 of of IN 478 481 the the DT 482 495 transcription transcription NN 496 504 activity activity NN 505 508 was be VBD 509 518 contained contain VBN 519 521 in in IN 522 523 a a DT 524 527 150 150 CD 528 530 bp bp NN 531 539 promoter promoter NN 540 548 fragment fragment NN 549 553 with with IN 554 561 binding bind VBG 562 567 sites site NNS 568 571 for for IN 572 585 transcription transcription NN 586 593 factors factor NNS 594 597 AP2 ap2 NN 597 598 , , , 599 602 Sp1 Sp1 NNP 603 606 and and CC 607 610 the the DT 611 629 erythroid-specific erythroid-specific JJ 630 636 GATA-1 gata-1 NN 636 637 . . . 638 641 The the DT 642 645 150 150 CD 646 648 bp bp NN 649 654 hEpoR hEpoR NNP 655 663 promoter promoter NN 664 673 exhibited exhibit VBD 674 678 high high JJ 679 682 and and CC 683 686 low low JJ 687 695 activity activity NN 696 698 in in IN 699 708 erythroid erythroid JJ 709 714 OCIM1 ocim1 NN 715 718 and and CC 719 723 K562 k562 NN 724 729 cells cell NNS 729 730 , , , 731 743 respectively respectively RB 743 744 , , , 745 755 reflecting reflect VBG 756 759 the the DT 760 764 high high JJ 765 768 and and CC 769 772 low low JJ 773 779 levels level NNS 780 782 of of IN 783 795 constitutive constitutive JJ 796 801 hEpoR hEpoR NNP 802 812 expression expression NN 812 813 . . . 814 817 The the DT 818 824 GATA-1 gata-1 NN 825 828 and and CC 829 832 Sp1 sp1 NN 833 840 binding binding NN 841 846 sites site NNS 847 849 in in IN 850 854 this this DT 855 863 promoter promoter NN 864 871 lacking lack VBG 872 873 a a DT 874 878 TATA TATA NNP 879 887 sequence sequence NN 888 892 were be VBD 893 902 necessary necessary JJ 903 906 for for IN 907 908 a a DT 909 913 high high JJ 914 919 level level NN 920 922 of of IN 923 936 transcription transcription NN 937 947 activation activation NN 947 948 . . . 949 960 Protein-DNA protein-dna JJ 961 968 binding binding NN 969 976 studies study NNS 977 986 suggested suggest VBD 987 991 that that IN 992 995 Sp1 Sp1 NNP 996 999 and and CC 1000 1003 two two CD 1004 1009 other other JJ 1010 1016 CCGCCC CCGCCC NNP 1017 1024 binding binding NN 1025 1033 proteins protein NNS 1034 1038 from from IN 1039 1048 erythroid erythroid JJ 1049 1052 and and CC 1053 1066 non-erythroid non-erythroid JJ 1067 1072 cells cell NNS 1073 1078 could could MD 1079 1083 bind bind VB 1084 1086 to to TO 1087 1090 the the DT 1091 1094 Sp1 sp1 NN 1095 1102 binding binding NN 1103 1108 motif motif NN 1108 1109 . . . 1110 1112 By by IN 1113 1123 increasing increase VBG 1124 1130 GATA-1 gata-1 NN 1131 1137 levels level NNS 1138 1141 via via IN 1142 1157 co-transfection co-transfection NN 1157 1158 , , , 1159 1161 we we PRP 1162 1166 were be VBD 1167 1171 able able JJ 1172 1174 to to TO 1175 1188 transactivate transactivate VB 1189 1192 the the DT 1193 1198 hEpoR hEpoR NNP 1199 1207 promoter promoter NN 1208 1210 in in IN 1211 1215 K562 k562 NN 1216 1221 cells cell NNS 1222 1225 and and CC 1226 1239 non-erythroid non-erythroid JJ 1240 1245 cells cell NNS 1245 1246 , , , 1247 1250 but but CC 1251 1254 not not RB 1255 1257 in in IN 1258 1261 the the DT 1262 1268 highly highly RB 1269 1275 active active JJ 1276 1281 OCIM1 ocim1 NN 1282 1287 cells cell NNS 1287 1288 , , , 1289 1297 although although IN 1298 1304 GATA-1 gata-1 NN 1305 1309 mRNA mrna NN 1310 1316 levels level NNS 1317 1321 were be VBD 1322 1332 comparable comparable JJ 1333 1335 in in IN 1336 1341 OCIM1 OCIM1 NNP 1342 1345 and and CC 1346 1350 K562 k562 NN 1350 1351 . . . 1352 1365 Interestingly interestingly RB 1365 1366 , , , 1367 1371 when when WRB 1372 1374 we we PRP 1375 1382 mutated mutate VBD 1383 1386 the the DT 1387 1390 Sp1 sp1 NN 1391 1395 site site NN 1395 1396 , , , 1397 1406 resulting result VBG 1407 1409 in in IN 1410 1411 a a DT 1412 1418 marked marked JJ 1419 1427 decrease decrease NN 1428 1430 in in IN 1431 1436 hEpoR hEpoR NNP 1437 1445 promoter promoter NN 1446 1454 activity activity NN 1454 1455 , , , 1456 1458 we we PRP 1459 1464 could could MD 1465 1472 restore restore VB 1473 1488 transactivation transactivation NN 1489 1491 by by IN 1492 1502 increasing increase VBG 1503 1509 GATA-1 gata-1 NN 1510 1516 levels level NNS 1517 1519 in in IN 1520 1525 OCIM1 ocim1 NN 1526 1531 cells cell NNS 1531 1532 . . . 1533 1538 These these DT 1539 1543 data datum NNS 1544 1551 suggest suggest VBP 1552 1556 that that IN 1557 1562 while while IN 1563 1569 GATA-1 gata-1 NN 1570 1573 can can MD 1574 1587 transactivate transactivate VB 1588 1591 the the DT 1592 1596 EpoR epor NN 1597 1605 promoter promoter NN 1605 1606 , , , 1607 1610 the the DT 1611 1616 level level NN 1617 1619 of of IN 1620 1625 hEpoR hEpoR NNP 1626 1630 gene gene NN 1631 1641 expression expression NN 1642 1646 does do VBZ 1647 1650 not not RB 1651 1657 depend depend VB 1658 1660 on on IN 1661 1667 GATA-1 gata-1 NN 1668 1673 alone alone RB 1673 1674 . . . 1675 1681 Rather rather RB 1681 1682 , , , 1683 1688 hEpoR hEpoR NNP 1689 1702 transcription transcription NN 1703 1711 activity activity NN 1712 1719 depends depend VBZ 1720 1722 on on IN 1723 1735 coordination coordination NN 1736 1743 between between IN 1744 1747 Sp1 sp1 NN 1748 1751 and and CC 1752 1758 GATA-1 gata-1 NN 1759 1763 with with IN 1764 1769 other other JJ 1770 1783 cell-specific cell-specific JJ 1784 1791 factors factor NNS 1791 1792 , , , 1793 1802 including include VBG 1803 1811 possibly possibly RB 1812 1817 other other JJ 1818 1826 Sp1-like sp1-like JJ 1827 1834 binding binding NN 1835 1843 proteins protein NNS 1843 1844 , , , 1845 1847 to to TO 1848 1855 provide provide VB 1856 1860 high high JJ 1861 1866 level level NN 1866 1867 , , , 1868 1883 tissue-specific tissue-specific JJ 1884 1894 expression expression NN 1894 1895 . . .