0 9 Different different JJ 10 18 sequence sequence NN 19 31 requirements requirement NNS 32 35 for for IN 36 46 expression expression NN 47 49 in in IN 50 59 erythroid erythroid JJ 60 63 and and CC 64 78 megakaryocytic megakaryocytic JJ 79 84 cells cell NNS 85 91 within within IN 92 93 a a DT 94 104 regulatory regulatory JJ 105 112 element element NN 113 121 upstream upstream JJ 122 124 of of IN 125 128 the the DT 129 135 GATA-1 gata-1 NN 136 140 gene gene NN 140 141 . . . 143 146 The the DT 147 165 lineage-restricted lineage-restricted JJ 166 179 transcription transcription NN 180 186 factor factor NN 187 193 GATA-1 gata-1 NN 194 196 is be VBZ 197 205 required require VBN 206 209 for for IN 210 225 differentiation differentiation NN 226 228 of of IN 229 238 erythroid erythroid JJ 239 242 and and CC 243 257 megakaryocytic megakaryocytic JJ 258 263 cells cell NNS 263 264 . . . 265 267 We we PRP 268 272 have have VBP 273 282 localized localize VBN 283 284 a a DT 285 288 317 317 CD 289 293 base base NN 294 298 pair pair NN 299 309 cis-acting cis-acting JJ 310 320 regulatory regulatory JJ 321 328 element element NN 328 329 , , , 330 332 HS HS NNP 333 334 I i CD 334 335 , , , 336 346 associated associate VBN 347 351 with with IN 352 353 a a DT 354 376 hematopoietic-specific hematopoietic-specific JJ 377 382 DNase dnase NN 383 384 I i CD 385 399 hypersensitive hypersensitive JJ 400 404 site site NN 404 405 , , , 406 411 which which WDT 412 416 lies lie VBZ 417 423 approx approx NN 423 424 . . . 425 428 3.7 3.7 CD 429 438 kilobases kilobas NNS 439 447 upstream upstream RB 448 450 of of IN 451 454 the the DT 455 461 murine murine JJ 462 484 hematopoietic-specific hematopoietic-specific JJ 485 491 GATA-1 gata-1 NN 492 494 IE ie NN 495 503 promoter promoter NN 503 504 . . . 505 507 HS HS NNP 508 509 I i CD 510 517 directs direct VBZ 518 528 high-level high-level JJ 529 539 expression expression NN 540 542 of of IN 543 551 reporter reporter NN 552 563 GATA-1/lacZ GATA-1/lacZ NNP 564 569 genes gene NNS 570 572 to to TO 573 582 primitive primitive JJ 583 586 and and CC 587 597 definitive definitive JJ 598 607 erythroid erythroid JJ 608 613 cells cell NNS 614 617 and and CC 618 632 megakaryocytes megakaryocyte NNS 633 635 in in IN 636 646 transgenic transgenic JJ 647 651 mice mouse NNS 651 652 . . . 653 664 Comparative comparative JJ 665 673 sequence sequence NN 674 682 analysis analysis NN 683 685 of of IN 686 688 HS HS NNP 689 690 I i CD 691 698 between between IN 699 704 human human JJ 705 708 and and CC 709 714 mouse mouse NN 715 720 shows show VBZ 721 727 approx approx NN 727 728 . . . 729 731 63 63 CD 731 732 % % NN 733 743 nucleotide nucleotide NN 744 752 identity identity NN 753 757 with with IN 758 759 a a DT 760 764 more more RBR 765 774 conserved conserve VBN 775 779 core core NN 780 782 of of IN 783 786 169 169 CD 787 791 base base NN 792 797 pairs pair NNS 798 799 ( ( ( 799 801 86 86 CD 801 802 % % NN 803 811 identity identity NN 811 812 ) ) ) 812 813 . . . 814 818 This this DT 819 823 core core NN 824 832 contains contain VBZ 833 834 a a DT 835 839 GATA GATA NNP 840 844 site site NN 845 854 separated separate VBN 855 857 by by IN 858 860 10 10 CD 861 865 base base NN 866 871 pairs pair NNS 872 876 from from IN 877 879 an an DT 880 885 E-box e-box NN 886 891 motif motif NN 891 892 . . . 893 896 The the DT 897 906 composite composite JJ 907 912 motif motif NN 913 918 binds bind VBZ 919 920 a a DT 921 934 multi-protein multi-protein JJ 935 957 hematopoietic-specific hematopoietic-specific JJ 958 971 transcription transcription NN 972 978 factor factor NN 979 986 complex complex NN 987 992 which which WDT 993 1001 includes include VBZ 1002 1008 GATA-1 gata-1 NN 1008 1009 , , , 1010 1019 SCL/tal-1 SCL/tal-1 NNP 1019 1020 , , , 1021 1024 E2A E2A NNP 1024 1025 , , , 1026 1030 Lmo2 lmo2 NN 1031 1034 and and CC 1035 1040 Ldb-1 Ldb-1 NNP 1040 1041 . . . 1042 1047 Point Point NNP 1048 1057 mutations mutation NNS 1058 1060 of of IN 1061 1064 the the DT 1065 1069 GATA GATA NNP 1070 1074 site site NN 1075 1084 abolishes abolish VBZ 1085 1087 HS hs NN 1088 1089 I i CD 1090 1098 function function NN 1098 1099 , , , 1100 1107 whereas whereas IN 1108 1116 mutation mutation NN 1117 1119 of of IN 1120 1123 the the DT 1124 1129 E-box e-box NN 1130 1135 motif motif NN 1136 1141 still still RB 1142 1148 allows allow VBZ 1149 1157 reporter reporter NN 1158 1162 gene gene NN 1163 1173 expression expression NN 1174 1176 in in IN 1177 1181 both both DT 1182 1190 lineages lineage NNS 1190 1191 . . . 1192 1198 Strict strict JJ 1199 1209 dependence dependence NN 1210 1212 of of IN 1213 1215 HS HS NNP 1216 1217 I i CD 1218 1226 activity activity NN 1227 1229 on on IN 1230 1231 a a DT 1232 1236 GATA GATA NNP 1237 1241 site site NN 1242 1249 implies imply VBZ 1250 1254 that that IN 1255 1263 assembly assembly NN 1264 1266 of of IN 1267 1268 a a DT 1269 1276 protein protein NN 1277 1284 complex complex NN 1285 1295 containing contain VBG 1296 1297 a a DT 1298 1309 GATA-factor gata-factor NN 1309 1310 , , , 1311 1321 presumably presumably RB 1322 1328 GATA-1 gata-1 NN 1329 1331 or or CC 1332 1338 GATA-2 gata-2 NN 1338 1339 , , , 1340 1342 is be VBZ 1343 1351 critical critical JJ 1352 1354 to to TO 1355 1365 activating activate VBG 1366 1368 or or CC 1369 1380 maintaining maintain VBG 1381 1384 its its PRP$ 1385 1393 function function NN 1393 1394 . . . 1395 1402 Further further JJ 1403 1413 dissection dissection NN 1414 1416 of of IN 1417 1420 the the DT 1421 1424 317 317 CD 1425 1429 base base NN 1430 1434 pair pair NN 1435 1441 region region NN 1442 1454 demonstrates demonstrate VBZ 1455 1459 that that IN 1459 1460 , , , 1461 1468 whereas whereas IN 1469 1472 all all DT 1473 1476 317 317 CD 1477 1481 base base NN 1482 1487 pairs pair NNS 1488 1491 are be VBP 1492 1500 required require VBN 1501 1504 for for IN 1505 1515 expression expression NN 1516 1518 in in IN 1519 1533 megakaryocytes megakaryocyte NNS 1533 1534 , , , 1535 1539 only only RB 1540 1543 the the DT 1544 1545 5 5 CD 1545 1546 ’ ' SYM 1547 1549 62 62 CD 1550 1554 base base NN 1555 1560 pairs pair NNS 1561 1564 are be VBP 1565 1571 needed need VBN 1572 1575 for for IN 1576 1594 erythroid-specific erythroid-specific JJ 1595 1603 reporter reporter NN 1604 1614 expression expression NN 1614 1615 . . . 1616 1621 These these DT 1622 1630 findings finding NNS 1631 1642 demonstrate demonstrate VBP 1643 1655 differential differential JJ 1656 1663 lineage lineage NN 1664 1676 requirements requirement NNS 1677 1680 for for IN 1681 1691 expression expression NN 1692 1698 within within IN 1699 1702 the the DT 1703 1705 HS HS NNP 1706 1707 I i CD 1708 1715 element element NN 1715 1716 . . .