0 10 Modulation modulation NN 11 13 of of IN 14 18 mRNA mrna NN 19 29 expression expression NN 30 32 of of IN 33 34 a a DT 35 40 novel novel JJ 41 46 human human JJ 47 64 myeloid-selective myeloid-selective JJ 65 79 CCAAT/enhancer ccaat/enhancer NN 80 87 binding binding NN 88 95 protein protein NN 96 100 gene gene NN 101 102 ( ( ( 102 107 C/EBP C/EBP NNP 108 115 epsilon epsilon NN 115 116 ) ) ) 116 117 . . . 119 124 Human human JJ 125 130 C/EBP C/EBP NNP 131 138 epsilon epsilon NN 139 141 is be VBZ 142 143 a a DT 144 149 newly newly RB 150 156 cloned clone VBN 157 161 gene gene NN 162 168 coding cod VBG 169 172 for for IN 173 174 a a DT 175 189 CCAAT/enhancer ccaat/enhancer NN 190 197 binding binding NN 198 205 protein protein NN 206 210 that that WDT 211 214 may may MD 215 217 be be VB 218 226 involved involve VBN 227 229 in in IN 230 233 the the DT 234 244 regulation regulation NN 245 247 of of IN 248 255 myeloid myeloid JJ 256 271 differentiation differentiation NN 271 272 . . . 273 276 Our our PRP$ 277 284 studies study NNS 285 291 showed show VBD 292 296 that that IN 297 303 levels level NNS 304 306 of of IN 307 312 C/EBP C/EBP NNP 313 320 epsilon epsilon NN 321 325 mRNA mRNA NNP 326 330 were be VBD 331 339 markedly markedly RB 340 349 increased increase VBN 350 352 in in IN 353 356 NB4 nb4 NN 357 362 cells cell NNS 363 364 ( ( ( 364 377 promyelocytic promyelocytic JJ 378 386 leukemia leukemia NN 387 391 line line NN 391 392 ) ) ) 392 393 , , , 394 401 because because IN 402 406 they they PRP 407 411 were be VBD 412 419 induced induce VBN 420 422 by by IN 423 428 9-cis 9-cis JJ 429 437 retinoic retinoic JJ 438 442 acid acid NN 443 444 ( ( ( 444 449 9-cis 9-cis NN 450 452 RA RA NNP 452 453 ) ) ) 454 456 to to TO 457 470 differentiate differentiate VB 471 478 towards towards IN 479 491 granulocytes granulocyte NNS 491 492 . . . 493 505 Accumulation Accumulation NNP 506 508 of of IN 509 514 C/EBP C/EBP NNP 515 522 epsilon epsilon NN 523 527 mRNA mRNA NNP 528 536 occurred occur VBD 537 539 as as RB 540 545 early early RB 546 548 as as IN 549 550 1 1 CD 551 555 hour hour NN 556 561 after after IN 562 570 exposure exposure NN 571 573 of of IN 574 577 NB4 nb4 NN 578 583 cells cell NNS 584 586 to to TO 587 592 9-cis 9-cis JJ 593 595 RA RA NNP 596 597 ( ( ( 597 598 5 5 CD 599 600 x x SYM 601 607 10(-7) 10(-7) CD 608 613 mol/L mol/l NN 613 614 ) ) ) 614 615 ; ; : 616 619 and and CC 620 622 at at IN 623 625 48 48 CD 626 631 hours hour NNS 631 632 , , , 633 639 levels level NNS 640 644 were be VBD 645 654 increased increase VBN 655 657 by by IN 658 666 5.1-fold 5.1-fold RB 666 667 . . . 668 681 Dose-response dose-response JJ 682 689 studies study NNS 690 696 showed show VBD 697 701 that that IN 702 708 10(-7) 10(-7) CD 709 711 to to TO 712 718 10(-6) 10(-6) CD 719 724 mol/L mol/l NN 725 730 9-cis 9-cis JJ 731 733 RA RA NNP 734 735 ( ( ( 735 737 12 12 CD 738 743 hours hour NNS 743 744 ) ) ) 745 753 resulted result VBD 754 756 in in IN 757 761 peak peak NN 762 768 levels level NNS 769 771 of of IN 772 777 C/EBP C/EBP NNP 778 785 epsilon epsilon NN 786 790 mRNA mRNA NNP 790 791 ; ; : 792 795 but but CC 796 800 even even RB 801 808 10(-10) 10(-10) CD 809 814 mol/L mol/l NN 815 820 9-cis 9-cis JJ 821 823 RA RA NNP 824 833 increased increase VBD 834 840 levels level NNS 841 843 of of IN 844 849 these these DT 850 861 transcripts transcript NNS 861 862 . . . 863 866 NB4 nb4 NN 867 872 cells cell NNS 873 886 pulse-exposed pulse-exposed JJ 887 888 ( ( ( 888 890 30 30 CD 891 898 minutes minute NNS 898 899 ) ) ) 900 902 to to TO 903 912 all-trans all-trans JJ 913 921 retinoic retinoic JJ 922 926 acid acid NN 927 928 ( ( ( 928 932 ATRA ATRA NNP 932 933 ) ) ) 933 934 , , , 935 941 washed wash VBN 941 942 , , , 943 946 and and CC 947 955 cultured culture VBN 956 957 ( ( ( 957 958 3 3 CD 959 963 days day NNS 963 964 ) ) ) 965 969 with with IN 970 976 either either CC 977 994 dimethylsulfoxide dimethylsulfoxide NN 995 996 ( ( ( 996 1000 DMSO DMSO NNP 1000 1001 ) ) ) 1002 1004 or or CC 1005 1018 hexamethylene hexamethylene NN 1019 1031 bisacetamide bisacetamide NN 1032 1033 ( ( ( 1033 1037 HMBA HMBA NNP 1037 1038 ) ) ) 1039 1042 had have VBD 1043 1044 a a DT 1045 1054 prominent prominent JJ 1055 1063 increase increase NN 1064 1066 in in IN 1067 1073 levels level NNS 1074 1076 of of IN 1077 1082 C/EBP C/EBP NNP 1083 1090 epsilon epsilon NN 1091 1095 mRNA mRNA NNP 1096 1099 and and CC 1100 1102 an an DT 1103 1111 increase increase NN 1112 1114 in in IN 1115 1127 granulocytic granulocytic JJ 1128 1143 differentiation differentiation NN 1143 1144 , , , 1145 1148 but but CC 1149 1157 exposure exposure NN 1158 1160 to to TO 1161 1167 either either CC 1168 1172 DMSO DMSO NNP 1173 1175 or or CC 1176 1180 HMBA HMBA NNP 1181 1186 alone alone RB 1187 1190 had have VBD 1191 1193 no no DT 1194 1200 effect effect NN 1201 1203 on on IN 1204 1208 base base NN 1209 1215 levels level NNS 1216 1218 of of IN 1219 1224 C/EBP C/EBP NNP 1225 1232 epsilon epsilon NN 1233 1236 and and CC 1237 1240 did do VBD 1241 1244 not not RB 1245 1251 induce induce VB 1252 1267 differentiation differentiation NN 1267 1268 . . . 1269 1295 Macrophage-differentiation Macrophage-differentiation NNP 1296 1298 of of IN 1299 1302 NB4 NB4 NNP 1303 1310 reduced reduce VBD 1311 1317 levels level NNS 1318 1320 of of IN 1321 1326 C/EBP C/EBP NNP 1327 1334 epsilon epsilon NN 1335 1339 mRNA mRNA NNP 1339 1340 . . . 1341 1348 Nuclear nuclear JJ 1349 1356 run-off run-off JJ 1357 1363 assays assay NNS 1364 1367 and and CC 1368 1377 half-life half-life NN 1378 1385 studies study NNS 1386 1392 showed show VBD 1393 1397 that that IN 1398 1410 accumulation accumulation NN 1411 1413 of of IN 1414 1419 C/EBP C/EBP NNP 1420 1427 epsilon epsilon NN 1428 1432 mRNA mRNA NNP 1433 1435 by by IN 1436 1441 9-cis 9-cis JJ 1442 1444 RA RA NNP 1445 1448 was be VBD 1449 1452 due due JJ 1453 1455 to to TO 1456 1464 enhanced enhance VBN 1465 1478 transcription transcription NN 1478 1479 . . . 1480 1491 Furthermore furthermore RB 1491 1492 , , , 1493 1497 this this DT 1498 1503 C/EBP C/EBP NNP 1504 1511 epsilon epsilon NN 1512 1516 mRNA mrna NN 1517 1529 accumulation accumulation NN 1530 1533 did do VBD 1534 1537 not not RB 1538 1545 require require VB 1546 1555 synthesis synthesis NN 1556 1558 of of IN 1559 1562 new new JJ 1563 1570 protein protein NN 1571 1578 factors factor NNS 1579 1586 because because IN 1587 1592 9-cis 9-cis JJ 1593 1595 RA RA NNP 1596 1603 induced induce VBD 1604 1609 C/EBP C/EBP NNP 1610 1617 epsilon epsilon NN 1618 1622 mRNA mrna NN 1623 1635 accumulation accumulation NN 1636 1638 in in IN 1639 1642 the the DT 1643 1650 absence absence NN 1651 1653 of of IN 1654 1657 new new JJ 1658 1665 protein protein NN 1666 1675 synthesis synthesis NN 1675 1676 . . . 1677 1681 ATRA ATRA NNP 1682 1686 also also RB 1687 1694 induced induce VBD 1695 1705 expression expression NN 1706 1708 of of IN 1709 1714 C/EBP C/EBP NNP 1715 1722 epsilon epsilon NN 1723 1730 protein protein NN 1731 1733 in in IN 1734 1737 NB4 nb4 NN 1738 1743 cells cell NNS 1743 1744 , , , 1745 1747 as as IN 1748 1753 shown show VBN 1754 1756 by by IN 1757 1764 Western western JJ 1765 1773 blotting blotting NN 1773 1774 . . . 1775 1777 In in IN 1778 1786 contrast contrast NN 1787 1789 to to TO 1790 1793 the the DT 1794 1802 increase increase NN 1803 1805 of of IN 1806 1811 C/EBP C/EBP NNP 1812 1819 epsilon epsilon NN 1820 1822 in in IN 1823 1828 9-cis 9-cis JJ 1829 1840 RA-mediated ra-mediated JJ 1841 1853 granulocytic granulocytic JJ 1854 1869 differentiation differentiation NN 1869 1870 , , , 1871 1874 the the DT 1875 1887 DMSO-induced dmso-induced JJ 1888 1903 differentiation differentiation NN 1904 1906 of of IN 1907 1912 HL-60 hl-60 NN 1913 1918 cells cell NNS 1919 1923 down down IN 1924 1927 the the DT 1928 1940 granulocytic granulocytic JJ 1941 1948 pathway pathway NN 1949 1952 was be VBD 1953 1963 associated associate VBN 1964 1968 with with IN 1969 1971 an an DT 1972 1979 initial initial JJ 1980 1989 reduction reduction NN 1990 1992 of of IN 1993 1998 C/EBP C/EBP NNP 1999 2006 epsilon epsilon NN 2007 2011 mRNA mrna NN 2012 2018 levels level NNS 2018 2019 . . . 2020 2022 In in IN 2023 2030 summary summary NN 2030 2031 , , , 2032 2034 we we PRP 2035 2039 have have VBP 2040 2050 discovered discover VBN 2051 2055 that that IN 2056 2066 expression expression NN 2067 2069 of of IN 2070 2075 C/EBP C/EBP NNP 2076 2083 epsilon epsilon NN 2084 2088 mRNA mRNA NNP 2089 2091 is be VBZ 2092 2100 markedly markedly RB 2101 2109 enhanced enhance VBN 2110 2112 as as IN 2113 2116 the the DT 2117 2120 NB4 nb4 NN 2121 2134 promyelocytes promyelocyte NNS 2135 2138 are be VBP 2139 2146 induced induce VBN 2147 2149 by by IN 2150 2159 retinoids retinoid NNS 2160 2162 to to TO 2163 2176 differentiate differentiate VB 2177 2184 towards towards IN 2185 2197 granulocytes granulocyte NNS 2197 2198 . . . 2199 2203 This this DT 2204 2213 induction induction NN 2214 2216 of of IN 2217 2222 C/EBP C/EBP NNP 2223 2230 epsilon epsilon NN 2231 2235 mRNA mrna NN 2236 2246 expression expression NN 2247 2249 is be VBZ 2250 2267 transcriptionally transcriptionally RB 2268 2276 mediated mediate VBN 2277 2280 and and CC 2281 2287 occurs occur VBZ 2288 2290 in in IN 2291 2294 the the DT 2295 2302 absence absence NN 2303 2305 of of IN 2306 2315 synthesis synthesis NN 2316 2318 of of IN 2319 2329 additional additional JJ 2330 2337 protein protein NN 2338 2345 factors factor NNS 2345 2346 . . . 2347 2349 We we PRP 2350 2357 suspect suspect VBP 2358 2362 that that IN 2363 2366 the the DT 2367 2372 C/EBP C/EBP NNP 2373 2380 epsilon epsilon NN 2381 2398 promoter/enhancer promoter/enhancer NN 2399 2407 contains contain VBZ 2408 2409 a a DT 2410 2418 retinoic retinoic JJ 2419 2432 acid-response acid-response JJ 2433 2440 element element NN 2441 2445 that that WDT 2446 2448 is be VBZ 2449 2457 directly directly RB 2458 2468 stimulated stimulate VBN 2469 2471 by by IN 2472 2481 retinoids retinoid NNS 2481 2482 . . .