0 7 Vitamin Vitamin NNP 8 11 D3- D3- NNP 12 15 and and CC 16 24 retinoic retinoic JJ 25 37 acid-induced acid-induced JJ 38 47 monocytic monocytic JJ 48 63 differentiation differentiation NN 63 64 : : : 65 77 interactions interaction NNS 78 85 between between IN 86 89 the the DT 90 100 endogenous endogenous JJ 101 108 vitamin vitamin NN 109 111 D3 d3 NN 112 120 receptor receptor NN 120 121 , , , 122 130 retinoic retinoic JJ 131 135 acid acid NN 136 145 receptors receptor NNS 145 146 , , , 147 150 and and CC 151 159 retinoid retinoid NN 160 161 X x NN 162 171 receptors receptor NNS 172 174 in in IN 175 180 U-937 u-937 NN 181 186 cells cell NNS 186 187 . . . 189 197 Retinoic retinoic JJ 198 202 acid acid NN 203 204 ( ( ( 204 206 RA RA NNP 206 207 ) ) ) 208 211 and and CC 212 216 1,25 1,25 CD 217 247 alpha-dihydroxycholecalciferol alpha-dihydroxycholecalciferol NN 248 249 ( ( ( 249 254 VitD3 VitD3 NNP 254 255 ) ) ) 256 259 are be VBP 260 266 potent potent JJ 267 277 regulators regulator NNS 278 280 of of IN 281 294 hematopoletic hematopoletic JJ 295 310 differentiation differentiation NN 310 311 . . . 312 315 Yet yet RB 315 316 , , , 317 323 little little JJ 324 326 is be VBZ 327 332 known know VBN 333 335 as as IN 336 338 to to TO 339 342 how how WRB 343 346 the the DT 347 349 RA RA NNP 350 353 and and CC 354 359 VitD3 VitD3 NNP 360 368 receptor receptor NN 369 376 network network NN 377 385 operates operate VBZ 386 388 in in IN 389 402 hematopoietic hematopoietic JJ 403 408 cells cell NNS 408 409 , , , 410 413 and and CC 414 421 whether whether IN 422 430 receptor receptor NN 431 443 interactions interaction NNS 444 447 can can MD 448 455 explain explain VB 456 459 the the DT 460 469 interplay interplay NN 470 477 between between IN 478 481 the the DT 482 485 RA- ra- NN 486 489 and and CC 490 505 VitD3-signaling vitd3-signaling JJ 506 514 pathways pathway NNS 515 521 during during IN 522 537 differentiation differentiation NN 537 538 . . . 539 548 Therefore therefore RB 548 549 , , , 550 552 we we PRP 553 561 analyzed analyze VBD 562 565 the the DT 566 576 expression expression NN 576 577 , , , 578 581 DNA DNA NNP 582 589 binding binding NN 589 590 , , , 591 594 and and CC 595 610 transcriptional transcriptional JJ 611 619 activity activity NN 620 622 of of IN 623 626 the the DT 627 637 endogenous endogenous JJ 638 640 RA RA NNP 641 644 and and CC 645 650 VitD3 vitd3 NN 651 660 receptors receptor NNS 661 662 [ [ ( 662 670 retinoic retinoic JJ 671 675 acid acid NN 676 685 receptors receptor NNS 686 687 ( ( ( 687 691 RARs RAR NNP 691 692 ) ) ) 692 693 , , , 694 702 retinoid retinoid JJ 703 704 X X NNP 705 714 receptors receptor NNS 715 716 ( ( ( 716 720 RXRs RXR NNP 720 721 ) ) ) 721 722 , , , 723 726 and and CC 727 732 VitD3 vitd3 NN 733 741 receptor receptor NN 742 743 ( ( ( 743 746 VDR VDR NNP 746 747 ) ) ) 747 748 ] ] ) 749 751 in in IN 752 755 the the DT 756 761 U-937 u-937 NN 762 766 cell cell NN 767 771 line line NN 771 772 , , , 773 775 in in IN 776 781 which which WDT 782 784 RA RA NNP 785 788 and and CC 789 794 VitD3 VitD3 NNP 795 801 induce induce VBP 802 810 distinct distinct JJ 811 820 monocytic monocytic JJ 821 836 differentiation differentiation NN 837 845 pathways pathway NNS 845 846 . . . 847 852 VitD3 vitd3 NN 853 862 induction induction NN 863 871 resulted result VBD 872 874 in in IN 875 878 the the DT 879 888 formation formation NN 889 891 of of IN 892 899 VDR/RXR VDR/RXR NNP 900 911 DNA-binding dna-binding JJ 912 921 complexes complex NNS 922 924 on on IN 925 929 both both CC 930 935 VitD3 vitd3 NN 936 944 response response NN 945 953 elements element NNS 954 957 and and CC 958 960 RA RA NNP 961 969 response response NN 970 978 elements element NNS 979 980 ( ( ( 980 985 RAREs RARE NNP 985 986 ) ) ) 986 987 . . . 988 995 However however RB 995 996 , , , 997 1012 transcriptional transcriptional JJ 1013 1023 activation activation NN 1024 1027 was be VBD 1028 1032 only only RB 1033 1041 observed observe VBN 1042 1046 from from IN 1047 1048 a a DT 1049 1054 VitD3 vitd3 NN 1055 1063 response response NN 1064 1078 element-driven element-driven JJ 1079 1087 reporter reporter NN 1088 1097 construct construct NN 1097 1098 . . . 1099 1106 Several several JJ 1107 1118 DNA-binding dna-binding JJ 1119 1128 complexes complex NNS 1129 1133 were be VBD 1134 1142 detected detect VBN 1143 1145 on on IN 1146 1151 RAREs rare NNS 1152 1154 in in IN 1155 1171 undifferentiated undifferentiated JJ 1172 1177 cells cell NNS 1177 1178 . . . 1179 1190 Stimulation stimulation NN 1191 1193 by by IN 1194 1196 RA RA NNP 1197 1205 resulted result VBD 1206 1208 in in IN 1209 1218 increased increase VBN 1219 1222 RAR RAR NNP 1223 1231 beta/RXR beta/RXR NNP 1232 1235 DNA DNA NNP 1236 1243 binding binding NN 1243 1244 , , , 1245 1254 activated activate VBN 1255 1269 RARE-dependent rare-dependent JJ 1270 1283 transcription transcription NN 1283 1284 , , , 1285 1288 and and CC 1289 1298 increased increase VBN 1299 1309 expression expression NN 1310 1312 of of IN 1313 1321 RAR-beta RAR-beta NNP 1321 1322 . . . 1323 1334 Concomitant concomitant JJ 1335 1346 stimulation stimulation NN 1347 1349 by by IN 1350 1355 VitD3 VitD3 NNP 1356 1365 inhibited inhibit VBD 1366 1369 the the DT 1370 1383 RA-stimulated ra-stimulated JJ 1384 1393 formation formation NN 1394 1396 of of IN 1397 1400 RAR RAR NNP 1401 1409 beta/RXR beta/RXR NNP 1410 1422 heterodimers heterodimer NNS 1422 1423 , , , 1424 1432 favoring favor VBG 1433 1440 VDR/RXR vdr/rxr NN 1441 1448 binding binding NN 1449 1451 to to TO 1452 1455 the the DT 1456 1460 RARE rare NN 1460 1461 . . . 1462 1466 Also also RB 1466 1467 , , , 1468 1473 VitD3 VitD3 NNP 1474 1483 inhibited inhibit VBD 1484 1487 the the DT 1488 1498 expression expression NN 1499 1501 of of IN 1502 1506 CD23 CD23 NNP 1507 1510 and and CC 1511 1516 CD49f CD49f NNP 1516 1517 , , , 1518 1532 characteristic characteristic JJ 1533 1540 markers marker NNS 1541 1543 of of IN 1544 1560 retinoid-induced retinoid-induced JJ 1561 1566 U-937 u-937 NN 1567 1571 cell cell NN 1572 1587 differentiation differentiation NN 1587 1588 . . . 1589 1591 In in IN 1592 1600 contrast contrast NN 1600 1601 , , , 1602 1609 neither neither CC 1610 1613 the the DT 1614 1627 RA-stimulated ra-stimulated JJ 1627 1628 , , , 1629 1642 RARE-mediated rare-mediated JJ 1643 1656 transcription transcription NN 1657 1660 nor nor CC 1661 1664 the the DT 1665 1672 induced induce VBN 1673 1681 RAR-beta RAR-beta NNP 1682 1692 expression expression NN 1693 1696 was be VBD 1697 1707 suppressed suppress VBN 1708 1710 by by IN 1711 1716 VitD3 VitD3 NNP 1716 1717 , , , 1718 1728 suggesting suggest VBG 1729 1733 that that IN 1734 1739 VitD3 VitD3 NNP 1740 1751 selectively selectively RB 1752 1761 inhibited inhibit VBD 1762 1765 the the DT 1766 1782 retinoid-induced retinoid-induced JJ 1783 1798 differentiation differentiation NN 1799 1806 program program NN 1807 1810 but but CC 1811 1814 not not RB 1815 1818 the the DT 1819 1832 RARE-mediated rare-mediated JJ 1833 1839 signal signal NN 1839 1840 . . . 1841 1846 These these DT 1847 1854 results result NNS 1855 1866 demonstrate demonstrate VBP 1867 1868 a a DT 1869 1876 complex complex JJ 1877 1881 role role NN 1882 1885 for for IN 1886 1891 VitD3 vitd3 NN 1892 1894 in in IN 1895 1904 modifying modify VBG 1905 1908 the the DT 1909 1917 retinoid retinoid NN 1918 1933 differentiation differentiation NN 1934 1941 pathway pathway NN 1942 1945 and and CC 1946 1949 may may MD 1950 1954 have have VB 1955 1967 implications implication NNS 1968 1971 for for IN 1972 1996 differentiation-inducing differentiation-inducing JJ 1997 2004 therapy therapy NN 2005 2007 of of IN 2008 2021 hematopoietic hematopoietic JJ 2022 2028 tumors tumor NNS 2028 2029 . . .