0 8 Multiple multiple JJ 9 29 prolactin-responsive prolactin-responsive JJ 30 38 elements element NNS 39 46 mediate mediate VBP 47 49 G1 G1 NNP 50 53 and and CC 54 55 S S NNP 56 61 phase phase NN 62 72 expression expression NN 73 75 of of IN 76 79 the the DT 80 90 interferon interferon NN 91 101 regulatory regulatory JJ 102 110 factor-1 factor-1 NN 111 115 gene gene NN 115 116 . . . 118 121 The the DT 122 132 interferon interferon NN 133 143 regulatory regulatory JJ 144 152 factor-1 factor-1 NN 153 154 ( ( ( 154 159 IRF-1 irf-1 NN 159 160 ) ) ) 161 165 gene gene NN 166 168 is be VBZ 169 173 both both CC 174 176 an an DT 177 192 immediate-early immediate-early JJ 193 195 G1 g1 NN 196 201 phase phase NN 202 206 gene gene NN 207 210 and and CC 211 213 an an DT 214 215 S S NNP 216 221 phase phase NN 222 226 gene gene NN 227 236 inducible inducible JJ 237 239 by by IN 240 243 PRL PRL NNP 244 246 in in IN 247 250 rat rat NN 251 254 Nb2 nb2 NN 255 256 T t NN 257 268 lymphocytes lymphocyte NNS 268 269 . . . 270 272 To to TO 273 283 understand understand VB 284 287 the the DT 288 297 mechanism mechanism NN 298 300 by by IN 301 306 which which WDT 307 310 PRL PRL NNP 311 320 regulates regulate VBZ 321 324 the the DT 325 333 biphasic biphasic JJ 334 344 expression expression NN 345 347 of of IN 348 353 IRF-1 irf-1 NN 353 354 , , , 355 357 we we PRP 358 364 cloned clone VBD 365 368 the the DT 369 372 rat rat NN 373 378 IRF-1 irf-1 NN 379 383 gene gene NN 384 387 and and CC 388 400 functionally functionally RB 401 414 characterized characterize VBD 415 418 the the DT 419 424 IRF-1 irf-1 NN 425 433 promoter promoter NN 433 434 . . . 435 439 Upon upon IN 440 452 transfection transfection NN 453 457 into into IN 458 461 Nb2 nb2 NN 462 463 T t NN 464 469 cells cell NNS 469 470 , , , 471 474 1.7 1.7 CD 475 484 kilobases kilobas NNS 485 486 ( ( ( 486 488 kb kb NN 488 489 ) ) ) 490 492 of of IN 493 498 IRF-1 irf-1 NN 499 510 5’-flanking 5'-flanking JJ 511 514 DNA dna NN 515 521 linked link VBN 522 524 to to TO 525 526 a a DT 527 542 chloramphenicol chloramphenicol NN 543 549 acetyl acetyl NN 550 561 transferase transferase NN 562 563 ( ( ( 563 566 CAT CAT NNP 566 567 ) ) ) 568 576 reporter reporter NN 577 581 gene gene NN 582 590 mediated mediate VBD 591 592 a a DT 593 600 30-fold 30-fold JJ 601 610 induction induction NN 611 613 of of IN 614 617 CAT CAT NNP 618 624 enzyme enzyme NN 625 633 activity activity NN 634 636 in in IN 637 645 response response NN 646 648 to to TO 649 651 24 24 CD 652 653 h h NN 654 656 of of IN 657 660 PRL PRL NNP 661 672 stimulation stimulation NN 672 673 . . . 674 682 Deletion deletion NN 683 690 mutants mutant NNS 691 701 containing contain VBG 702 705 1.3 1.3 CD 705 706 , , , 707 710 0.6 0.6 CD 710 711 , , , 712 715 and and CC 716 719 0.2 0.2 CD 720 722 kb kb NN 723 734 5’-flanking 5'-flanking JJ 735 738 DNA dna NN 739 743 were be VBD 744 757 incrementally incrementally RB 758 762 less less RBR 763 780 transcriptionally transcriptionally RB 781 787 active active JJ 787 788 , , , 789 797 although although IN 798 801 0.2 0.2 CD 802 804 kb kb NN 805 810 still still RB 811 819 mediated mediate VBD 820 821 a a DT 822 829 12-fold 12-fold JJ 830 839 induction induction NN 840 842 by by IN 843 846 PRL PRL NNP 846 847 . . . 848 851 The the DT 852 860 sequence sequence NN 861 868 between between IN 869 873 -1.7 -1.7 CD 874 877 and and CC 878 882 -0.2 -0.2 CD 883 885 kb kb NN 886 892 linked link VBN 893 895 to to TO 896 897 a a DT 898 910 heterologous heterologous JJ 911 920 thymidine thymidine NN 921 927 kinase kinase NNP 928 936 promoter promoter NN 937 943 failed fail VBD 944 946 to to TO 947 954 respond respond VB 955 957 to to TO 958 961 PRL PRL NNP 962 973 stimulation stimulation NN 973 974 , , , 975 985 suggesting suggest VBG 986 990 that that IN 991 994 the the DT 995 1003 activity activity NN 1004 1006 of of IN 1007 1015 upstream upstream JJ 1016 1019 PRL prl NN 1020 1028 response response NN 1029 1037 elements element NNS 1038 1041 may may MD 1042 1049 require require VB 1050 1052 an an DT 1053 1064 interaction interaction NN 1065 1069 with with IN 1070 1087 promoter-proximal promoter-proximal JJ 1088 1096 elements element NNS 1096 1097 . . . 1098 1100 By by IN 1101 1109 assaying assay VBG 1110 1113 CAT CAT NNP 1114 1120 enzyme enzyme NN 1121 1129 activity activity NN 1130 1136 across across IN 1137 1138 a a DT 1139 1143 24-h 24-h JJ 1144 1147 PRL PRL NNP 1148 1157 induction induction NN 1158 1162 time time NN 1163 1169 course course NN 1169 1170 , , , 1171 1173 we we PRP 1174 1178 were be VBD 1179 1183 able able JJ 1184 1186 to to TO 1187 1193 assign assign VB 1194 1196 G1 G1 NNP 1197 1200 vs. vs. IN 1201 1202 S S NNP 1203 1208 phase phase NN 1209 1212 PRL prl NN 1213 1222 responses response NNS 1223 1225 of of IN 1226 1229 the the DT 1230 1235 IRF-1 irf-1 NN 1236 1240 gene gene NN 1241 1243 to to TO 1244 1253 different different JJ 1254 1261 regions region NNS 1262 1264 of of IN 1265 1268 the the DT 1269 1274 IRF-1 irf-1 NN 1275 1286 5’-flanking 5'-flanking JJ 1287 1290 and and CC 1291 1299 promoter promoter NN 1300 1303 DNA dna NN 1303 1304 . . . 1305 1308 The the DT 1309 1315 0.2-kb 0.2-kb JJ 1316 1323 IRF-CAT IRF-CAT NNP 1324 1333 construct construct NN 1334 1337 was be VBD 1338 1345 induced induce VBN 1346 1348 by by IN 1349 1352 PRL PRL NNP 1353 1364 stimulation stimulation NN 1365 1371 during during IN 1372 1375 the the DT 1376 1378 G1 g1 NN 1379 1384 phase phase NN 1385 1387 of of IN 1388 1391 the the DT 1392 1396 cell cell NN 1397 1402 cycle cycle NN 1402 1403 . . . 1404 1406 In in IN 1407 1415 contrast contrast NN 1415 1416 , , , 1417 1420 the the DT 1421 1427 1.7-kb 1.7-kb JJ 1428 1435 IRF-CAT IRF-CAT NNP 1436 1445 construct construct NN 1446 1449 was be VBD 1450 1459 inducible inducible JJ 1460 1462 by by IN 1463 1466 PRL PRL NNP 1467 1473 during during IN 1474 1478 both both CC 1479 1481 G1 G1 NNP 1482 1485 and and CC 1486 1487 S S NNP 1488 1493 phase phase NN 1494 1496 of of IN 1497 1500 the the DT 1501 1505 cell cell NN 1506 1511 cycle cycle NN 1511 1512 . . . 1513 1518 Hence hence RB 1518 1519 , , , 1520 1523 the the DT 1524 1535 PRL-induced prl-induced JJ 1536 1544 biphasic biphasic JJ 1545 1555 expression expression NN 1556 1558 of of IN 1559 1562 the the DT 1563 1568 IRF-1 irf-1 NN 1569 1573 gene gene NN 1574 1581 appears appear VBZ 1582 1584 to to TO 1585 1587 be be VB 1588 1598 controlled control VBN 1599 1601 by by IN 1602 1610 separate separate JJ 1611 1625 PRL-responsive prl-responsive JJ 1626 1634 elements element NNS 1634 1635 : : : 1636 1644 elements element NNS 1645 1647 in in IN 1648 1651 the the DT 1652 1657 first first JJ 1658 1661 0.2 0.2 CD 1662 1664 kb kb NN 1665 1667 of of IN 1668 1671 the the DT 1672 1677 IRF-1 irf-1 NN 1678 1686 promoter promoter NN 1687 1693 region region NN 1694 1697 act act VBP 1698 1704 during during IN 1705 1710 early early JJ 1711 1721 activation activation NN 1721 1722 , , , 1723 1726 and and CC 1727 1735 elements element NNS 1736 1743 between between IN 1744 1747 0.2 0.2 CD 1748 1751 and and CC 1752 1755 1.7 1.7 CD 1756 1758 kb kb NN 1759 1762 act act VBP 1763 1765 in in IN 1766 1773 concert concert NN 1774 1778 with with IN 1779 1782 the the DT 1783 1791 proximal proximal JJ 1792 1798 0.2-kb 0.2-kb JJ 1799 1805 region region NN 1806 1812 during during IN 1813 1814 S S NNP 1815 1820 phase phase NN 1821 1832 progression progression NN 1832 1833 . . .