0 15 Transcriptional transcriptional JJ 16 26 regulation regulation NN 27 29 of of IN 30 33 the the DT 34 42 ferritin ferritin NN 43 54 heavy-chain heavy-chain JJ 55 59 gene gene NN 59 60 : : : 61 64 the the DT 65 73 activity activity NN 74 76 of of IN 77 80 the the DT 81 86 CCAAT CCAAT NNP 87 94 binding binding NN 95 101 factor factor NN 102 106 NF-Y nf-y NN 107 109 is be VBZ 110 119 modulated modulate VBN 120 122 in in IN 123 135 heme-treated heme-treated JJ 136 142 Friend Friend NNP 143 151 leukemia leukemia NN 152 157 cells cell NNS 158 161 and and CC 162 168 during during IN 169 191 monocyte-to-macrophage monocyte-to-macrophage JJ 192 207 differentiation differentiation NN 207 208 . . . 210 213 The the DT 214 222 ferritin ferritin NN 223 230 H-chain H-chain NNP 231 235 gene gene NN 236 244 promoter promoter NN 245 255 regulation regulation NN 256 259 was be VBD 260 268 analyzed analyze VBN 269 271 in in IN 272 284 heme-treated heme-treated JJ 285 291 Friend Friend NNP 292 300 leukemia leukemia NN 301 306 cells cell NNS 307 308 ( ( ( 308 312 FLCs FLC NNPS 312 313 ) ) ) 314 317 and and CC 318 324 during during IN 325 347 monocyte-to-macrophage monocyte-to-macrophage JJ 348 363 differentiation differentiation NN 363 364 . . . 365 367 In in IN 368 371 the the DT 372 380 majority majority NN 381 383 of of IN 384 388 cell cell NN 389 394 lines line NNS 395 402 studied study VBN 402 403 , , , 404 407 the the DT 408 418 regulation regulation NN 419 421 of of IN 422 430 ferritin ferritin NN 431 441 expression expression NN 442 445 was be VBD 446 453 exerted exert VBN 454 460 mostly mostly RB 461 463 at at IN 464 467 the the DT 468 481 translational translational JJ 482 487 level level NN 487 488 . . . 489 496 However however RB 496 497 , , , 498 500 in in IN 501 516 differentiating differentiate VBG 517 526 erythroid erythroid JJ 527 532 cells cell NNS 532 533 , , , 534 539 which which WDT 540 544 must must MD 545 556 incorporate incorporate VB 557 561 high high JJ 562 568 levels level NNS 569 571 of of IN 572 576 iron iron NN 577 579 to to TO 580 587 sustain sustain VB 588 598 hemoglobin hemoglobin NN 599 608 synthesis synthesis NN 608 609 , , , 610 613 and and CC 614 616 in in IN 617 628 macrophages macrophage NNS 628 629 , , , 630 635 which which WDT 636 639 are be VBP 640 648 involved involve VBN 649 651 in in IN 652 656 iron iron NN 657 664 storage storage NN 664 665 , , , 666 681 transcriptional transcriptional JJ 682 692 regulation regulation NN 693 699 seemed seem VBD 700 702 to to TO 703 705 be be VB 706 707 a a DT 708 716 relevant relevant JJ 717 726 mechanism mechanism NN 726 727 . . . 728 730 We we PRP 731 735 show show VBP 736 740 here here RB 741 745 that that IN 746 749 the the DT 750 757 minimum minimum JJ 758 764 region region NN 765 767 of of IN 768 771 the the DT 772 780 ferritin ferritin NN 781 787 H-gene H-gene NNP 788 796 promoter promoter NN 797 801 that that WDT 802 804 is be VBZ 805 809 able able JJ 810 812 to to TO 813 819 confer confer VB 820 835 transcriptional transcriptional JJ 836 846 regulation regulation NN 847 849 by by IN 850 854 heme heme NN 855 857 in in IN 858 862 FLCs flc NNS 863 865 to to TO 866 867 a a DT 868 876 reporter reporter NN 877 881 gene gene NN 882 884 is be VBZ 885 887 77 77 CD 888 899 nucleotides nucleotide NNS 900 908 upstream upstream RB 909 911 of of IN 912 915 the the DT 916 920 TATA TATA NNP 921 924 box box NN 924 925 . . . 926 930 This this DT 931 934 cis cis NN 935 942 element element NN 943 948 binds bind VBZ 949 950 a a DT 951 958 protein protein NN 959 966 complex complex NN 967 975 referred refer VBN 976 978 to to TO 979 981 as as IN 982 985 HRF HRF NNP 986 987 ( ( ( 987 1002 heme-responsive heme-responsive JJ 1003 1009 factor factor NN 1009 1010 ) ) ) 1010 1011 , , , 1012 1017 which which WDT 1018 1020 is be VBZ 1021 1028 greatly greatly RB 1029 1037 enhanced enhance VBN 1038 1042 both both CC 1043 1045 in in IN 1046 1058 heme-treated heme-treated JJ 1059 1063 FLCs flc NNS 1064 1067 and and CC 1068 1074 during during IN 1075 1097 monocyte-to-macrophage monocyte-to-macrophage JJ 1098 1113 differentiation differentiation NN 1113 1114 . . . 1115 1118 The the DT 1119 1124 CCAAT CCAAT NNP 1125 1132 element element NN 1133 1140 present present JJ 1141 1143 in in IN 1144 1151 reverse reverse JJ 1152 1163 orientation orientation NN 1164 1166 in in IN 1167 1171 this this DT 1172 1180 promoter promoter NN 1181 1187 region region NN 1188 1190 of of IN 1191 1194 the the DT 1195 1203 ferritin ferritin NN 1204 1211 H-chain h-chain JJ 1212 1216 gene gene NN 1217 1219 is be VBZ 1220 1229 necessary necessary JJ 1230 1233 for for IN 1234 1241 binding binding NN 1242 1245 and and CC 1246 1249 for for IN 1250 1254 gene gene NN 1255 1263 activity activity NN 1263 1264 , , , 1265 1270 since since IN 1271 1272 a a DT 1273 1279 single single JJ 1280 1285 point point NN 1286 1294 mutation mutation NN 1295 1297 is be VBZ 1298 1302 able able JJ 1303 1305 to to TO 1306 1313 abolish abolish VB 1314 1317 the the DT 1318 1325 binding binding NN 1326 1328 of of IN 1329 1332 HRF HRF NNP 1333 1336 and and CC 1337 1340 the the DT 1341 1356 transcriptional transcriptional JJ 1357 1365 activity activity NN 1366 1368 in in IN 1369 1380 transfected transfecte VBN 1381 1386 cells cell NNS 1386 1387 . . . 1388 1390 By by IN 1391 1402 competition competition NN 1403 1414 experiments experiment NNS 1415 1418 and and CC 1419 1429 supershift supershift NN 1430 1436 assays assay NNS 1436 1437 , , , 1438 1440 we we PRP 1441 1451 identified identify VBD 1452 1455 the the DT 1456 1463 induced induce VBN 1464 1467 HRF hrf NN 1468 1470 as as IN 1471 1481 containing contain VBG 1482 1484 at at IN 1485 1490 least least JJS 1491 1494 the the DT 1495 1505 ubiquitous ubiquitous JJ 1506 1519 transcription transcription NN 1520 1526 factor factor NN 1527 1531 NF-Y nf-y NN 1531 1532 . . . 1533 1537 NF-Y NF-Y NNP 1538 1540 is be VBZ 1541 1547 formed form VBN 1548 1550 by by IN 1551 1556 three three CD 1557 1565 subunits subunit NNS 1565 1566 , , , 1567 1568 A A NNP 1568 1569 , , , 1570 1571 B B NNP 1571 1572 , , , 1573 1576 and and CC 1577 1578 C C NNP 1578 1579 , , , 1580 1583 all all DT 1584 1586 of of IN 1587 1592 which which WDT 1593 1596 are be VBP 1597 1606 necessary necessary JJ 1607 1610 for for IN 1611 1614 DNA DNA NNP 1615 1622 binding binding NN 1622 1623 . . . 1624 1638 Cotransfection cotransfection NN 1639 1643 with with IN 1644 1645 a a DT 1646 1659 transdominant transdominant JJ 1660 1668 negative negative JJ 1669 1675 mutant mutant NN 1676 1678 of of IN 1679 1682 the the DT 1683 1688 NF-YA NF-YA NNP 1689 1696 subunit subunit NN 1697 1706 abolishes abolish VBZ 1707 1710 the the DT 1711 1726 transcriptional transcriptional JJ 1727 1737 activation activation NN 1738 1740 by by IN 1741 1745 heme heme NN 1745 1746 , , , 1747 1757 indicating indicate VBG 1758 1762 that that IN 1763 1767 NF-Y NF-Y NNP 1768 1773 plays play VBZ 1774 1776 an an DT 1777 1786 essential essential JJ 1787 1791 role role NN 1792 1794 in in IN 1795 1799 this this DT 1800 1810 activation activation NN 1810 1811 . . . 1812 1814 We we PRP 1815 1819 have have VBP 1820 1824 also also RB 1825 1833 observed observe VBN 1834 1835 a a DT 1836 1848 differential differential JJ 1849 1859 expression expression NN 1860 1862 of of IN 1863 1866 the the DT 1867 1872 NF-YA NF-YA NNP 1873 1880 subunit subunit NN 1881 1883 in in IN 1884 1896 heme-treated heme-treated JJ 1897 1900 and and CC 1901 1908 control control NN 1909 1913 FLCs flc NNS 1914 1917 and and CC 1918 1924 during during IN 1925 1947 monocyte-to-macrophage monocyte-to-macrophage JJ 1948 1963 differentiation differentiation NN 1963 1964 . . .