0 15 Tissue-specific tissue-specific JJ 16 26 expression expression NN 27 29 of of IN 30 33 the the DT 34 42 platelet platelet NN 43 48 GPIIb GPIIb NNP 49 53 gene gene NN 53 54 . . . 56 59 One one CD 60 62 of of IN 63 66 the the DT 67 72 major major JJ 73 83 objectives objective NNS 84 86 in in IN 87 90 the the DT 91 96 study study NN 97 99 of of IN 100 114 thrombogenesis thrombogenesis NN 115 117 is be VBZ 118 120 to to TO 121 130 determine determine VB 131 134 the the DT 135 145 mechanisms mechanism NNS 146 148 by by IN 149 154 which which WDT 155 156 a a DT 157 170 hematopoietic hematopoietic JJ 171 181 progenitor progenitor NN 182 184 is be VBZ 185 194 activated activate VBN 195 198 and and CC 199 208 committed commit VBN 209 211 to to TO 212 215 the the DT 216 230 megakaryocytic megakaryocytic JJ 231 238 lineage lineage NN 238 239 . . . 240 246 Recent recent JJ 247 258 development development NN 259 261 of of IN 262 269 primary primary JJ 270 278 cultures culture NNS 279 281 of of IN 282 287 human human JJ 288 302 megakaryocytes megakaryocyte NNS 303 306 and and CC 307 310 the the DT 311 320 molecular molecular JJ 321 328 cloning cloning NN 329 331 of of IN 332 337 genes gene NNS 338 342 that that WDT 343 346 are be VBP 347 355 specific specific JJ 356 358 to to TO 359 363 this this DT 364 371 lineage lineage NN 372 377 offer offer VBP 378 381 the the DT 382 393 possibility possibility NN 394 396 of of IN 397 404 getting get VBG 405 409 some some DT 410 418 insights insight NNS 419 423 into into IN 424 427 the the DT 428 435 genetic genetic JJ 436 446 mechanisms mechanism NNS 447 451 that that WDT 452 459 control control VBP 460 480 megakaryocytopoiesis megakaryocytopoiesis NN 480 481 . . . 482 485 One one CD 486 490 gene gene NN 491 493 of of IN 494 502 interest interest NN 503 505 is be VBZ 506 509 the the DT 510 522 glycoprotein glycoprotein NN 523 526 IIb IIb NNP 527 528 ( ( ( 528 533 GPIIb GPIIb NNP 533 534 ) ) ) 535 539 gene gene NN 539 540 ; ; : 541 546 GPIIb GPIIb NNP 546 547 , , , 548 551 the the DT 552 557 alpha alpha NN 558 565 subunit subunit NN 566 568 of of IN 569 572 the the DT 573 581 platelet platelet NN 582 593 cytoadhesin cytoadhesin NN 594 604 GPIIb-IIIa GPIIb-IIIa NNP 604 605 , , , 606 608 is be VBZ 609 617 produced produce VBN 618 620 in in IN 621 635 megakaryocytes megakaryocyte NNS 636 638 at at IN 639 641 an an DT 642 647 early early JJ 648 653 stage stage NN 654 656 of of IN 657 660 the the DT 661 676 differentiation differentiation NN 676 677 , , , 678 685 whereas whereas IN 686 689 the the DT 690 695 other other JJ 696 703 subunit subunit NN 704 706 of of IN 707 711 this this DT 712 719 complex complex NN 719 720 , , , 721 727 GPIIIa GPIIIa NNP 727 728 , , , 729 731 is be VBZ 732 741 expressed express VBN 742 744 in in IN 745 750 other other JJ 751 756 cells cell NNS 756 757 . . . 758 761 For for IN 762 767 these these DT 768 775 reasons reason NNS 775 776 , , , 777 780 the the DT 781 792 5’-flanking 5'-flanking JJ 793 799 region region NN 800 802 of of IN 803 806 the the DT 807 812 GPIIb GPIIb NNP 813 817 gene gene NN 818 821 was be VBD 822 826 used use VBN 827 829 to to TO 830 838 identify identify VB 839 842 the the DT 843 850 regions region NNS 851 855 that that WDT 856 864 interact interact VBP 865 869 with with IN 870 881 DNA-binding dna-binding JJ 882 889 nuclear nuclear JJ 890 897 factors factor NNS 897 898 . . . 899 900 A a DT 901 909 fragment fragment NN 910 919 extending extend VBG 920 924 from from IN 925 929 -643 -643 CD 930 932 to to TO 933 936 +33 +33 CD 937 939 is be VBZ 940 947 capable capable JJ 948 950 of of IN 951 962 controlling control VBG 963 966 the the DT 967 982 tissue-specific tissue-specific JJ 983 993 expression expression NN 994 996 of of IN 997 1000 the the DT 1001 1004 CAT CAT NNP 1005 1009 gene gene NN 1010 1012 in in IN 1013 1025 transfection transfection NN 1026 1037 experiments experiment NNS 1037 1038 . . . 1039 1045 Within within IN 1046 1050 this this DT 1051 1057 region region NN 1057 1058 , , , 1059 1061 we we PRP 1062 1066 have have VBP 1067 1077 identified identify VBN 1078 1085 several several JJ 1086 1095 sequences sequence NNS 1096 1100 that that WDT 1101 1104 are be VBP 1105 1115 implicated implicate VBN 1116 1118 in in IN 1119 1122 DNA DNA NNP 1123 1130 protein protein NN 1131 1143 interactions interaction NNS 1144 1146 as as IN 1147 1152 shown show VBN 1153 1155 in in IN 1156 1161 DNAse DNAse NNP 1162 1163 I i NN 1164 1174 footprints footprint NNS 1175 1178 and and CC 1179 1182 gel gel NN 1183 1191 mobility mobility NN 1192 1197 shift shift NN 1198 1204 assays assay NNS 1204 1205 . . . 1206 1209 One one CD 1210 1216 region region NN 1216 1217 , , , 1218 1226 centered center VBN 1227 1229 at at IN 1230 1233 -54 -54 CD 1233 1234 , , , 1235 1237 is be VBZ 1238 1245 similar similar JJ 1246 1248 to to TO 1249 1250 a a DT 1251 1258 nuclear nuclear JJ 1259 1265 factor factor NN 1266 1276 E1-binding e1-binding JJ 1277 1281 site site NN 1281 1282 , , , 1283 1286 and and CC 1287 1288 a a DT 1289 1295 region region NN 1296 1303 located located JJ 1304 1306 at at IN 1307 1315 position position NN 1316 1320 -233 -233 CD 1321 1329 contains contain VBZ 1330 1331 a a DT 1332 1337 CCAAT ccaat NN 1338 1343 motif motif NN 1343 1344 . . . 1345 1348 Two two CD 1349 1356 domains domain NNS 1357 1365 centered center VBN 1366 1368 at at IN 1369 1378 positions position NNS 1379 1383 -345 -345 CD 1384 1387 and and CC 1388 1392 -540 -540 CD 1392 1393 , , , 1394 1406 respectively respectively RB 1406 1407 , , , 1408 1412 bind bind VBP 1413 1421 proteins protein NNS 1422 1426 that that WDT 1427 1430 are be VBP 1431 1438 present present JJ 1439 1441 in in IN 1442 1456 megakaryocytic megakaryocytic JJ 1457 1462 cells cell NNS 1463 1466 and and CC 1467 1477 nonrelated nonrelated JJ 1478 1483 cells cell NNS 1484 1486 as as RB 1487 1491 well well RB 1491 1492 . . . 1493 1500 Finally finally RB 1500 1501 , , , 1502 1505 two two CD 1506 1511 other other JJ 1512 1519 domains domain NNS 1519 1520 , , , 1521 1528 located located JJ 1529 1531 at at IN 1532 1541 positions position NNS 1542 1546 -460 -460 CD 1547 1550 and and CC 1551 1555 -510 -510 CD 1555 1556 , , , 1557 1565 interact interact VBP 1566 1570 with with IN 1571 1579 proteins protein NNS 1580 1584 that that WDT 1585 1588 are be VBP 1589 1593 only only RB 1594 1601 present present JJ 1602 1604 in in IN 1605 1619 megakaryocytic megakaryocytic JJ 1620 1625 cells cell NNS 1625 1626 . . . 1627 1629 In in IN 1630 1638 addition addition NN 1638 1639 , , , 1640 1648 deletion deletion NN 1649 1651 of of IN 1652 1655 the the DT 1656 1662 region region NN 1663 1673 containing contain VBG 1674 1679 these these DT 1680 1683 two two CD 1684 1691 domains domain NNS 1692 1699 results result VBZ 1700 1702 in in IN 1703 1704 a a DT 1705 1716 significant significant JJ 1717 1725 decrease decrease NN 1726 1728 of of IN 1729 1732 the the DT 1733 1741 promoter promoter NN 1742 1750 activity activity NN 1750 1751 . . . 1752 1754 It it PRP 1755 1757 is be VBZ 1758 1762 very very RB 1763 1769 likely likely JJ 1770 1774 that that IN 1775 1780 these these DT 1781 1788 domains domain NNS 1789 1793 bind bind VBP 1794 1816 megakaryocyte-specific megakaryocyte-specific JJ 1817 1824 nuclear nuclear JJ 1825 1833 proteins protein NNS 1834 1840 acting act VBG 1841 1843 as as IN 1844 1852 positive positive JJ 1853 1866 transcription transcription NN 1867 1874 factors factor NNS 1874 1875 . . .