0 1 A a DT 2 17 transcriptional transcriptional JJ 18 28 regulatory regulatory JJ 29 36 element element NN 37 39 is be VBZ 40 50 associated associate VBN 51 55 with with IN 56 57 a a DT 58 81 nuclease-hypersensitive nuclease-hypersensitive JJ 82 86 site site NN 87 89 in in IN 90 93 the the DT 94 97 pol pol NN 98 102 gene gene NN 103 105 of of IN 106 111 human human JJ 112 128 immunodeficiency immunodeficiency NN 129 134 virus virus NN 135 139 type type NN 140 141 1 1 CD 141 142 . . . 144 152 Analysis Analysis NNP 153 155 of of IN 156 159 the the DT 160 169 chromatin chromatin NN 170 182 organization organization NN 183 185 of of IN 186 189 the the DT 190 200 integrated integrate VBN 201 206 human human JJ 207 223 immunodeficiency immunodeficiency NN 224 229 virus virus NN 230 234 type type NN 235 236 1 1 CD 237 238 ( ( ( 238 243 HIV-1 HIV-1 NNP 243 244 ) ) ) 245 251 genome genome NN 252 255 has have VBZ 256 266 previously previously RB 267 275 revealed reveal VBN 276 277 a a DT 278 283 major major JJ 284 296 constitutive constitutive JJ 297 302 DNase DNase NNP 303 319 I-hypersensitive i-hypersensitive JJ 320 324 site site NN 325 335 associated associate VBN 336 340 with with IN 341 344 the the DT 345 348 pol pol NN 349 353 gene gene NN 354 355 ( ( ( 355 357 E. E. NNP 358 364 Verdin Verdin NNP 364 365 , , , 366 368 J. J. NNP 369 375 Virol. Virol. NNP 376 388 65:6790-6799 65:6790-6799 CD 388 389 , , , 390 394 1991 1991 CD 394 395 ) ) ) 395 396 . . . 397 399 In in IN 400 403 the the DT 404 411 present present JJ 412 418 report report NN 418 419 , , , 420 435 high-resolution high-resolution JJ 436 443 mapping mapping NN 444 446 of of IN 447 451 this this DT 452 456 site site NN 457 461 with with IN 462 467 DNase DNase NNP 468 469 I i CD 470 473 and and CC 474 485 micrococcal micrococcal JJ 486 494 nuclease nuclease NN 495 505 identified identify VBD 506 507 a a DT 508 523 nucleosome-free nucleosome-free JJ 524 530 region region NN 531 539 centered center VBN 540 546 around around IN 547 558 nucleotides nucleotide NNS 559 560 ( ( ( 560 562 nt nt NN 562 563 ) ) ) 564 568 4490 4490 CD 569 571 to to TO 572 576 4766 4766 CD 576 577 . . . 578 579 A a DT 580 586 500-bp 500-bp JJ 587 595 fragment fragment NN 596 608 encompassing encompass VBG 609 613 this this DT 614 628 hypersensitive hypersensitive JJ 629 633 site site NN 634 635 ( ( ( 635 637 nt nt NNS 638 642 4481 4481 CD 643 645 to to TO 646 650 4982 4982 CD 650 651 ) ) ) 652 661 exhibited exhibit VBD 662 685 transcription-enhancing transcription-enhancing JJ 686 694 activity activity NN 695 696 ( ( ( 696 700 two- two- CD 701 703 to to TO 704 713 threefold threefold JJ 713 714 ) ) ) 715 719 when when WRB 720 722 it it PRP 723 726 was be VBD 727 733 cloned clone VBN 734 736 in in IN 737 740 its its PRP$ 741 748 natural natural JJ 749 757 position position NN 758 762 with with IN 763 770 respect respect NN 771 773 to to TO 774 777 the the DT 778 783 HIV-1 HIV-1 NNP 784 792 promoter promoter NN 793 798 after after IN 799 808 transient transient JJ 809 821 transfection transfection NN 822 824 in in IN 825 829 U937 U937 NNP 830 833 and and CC 834 837 CEM CEM NNP 838 843 cells cell NNS 843 844 . . . 845 850 Using use VBG 851 853 in in FW 854 859 vitro vitro FW 860 872 footprinting footprinting NN 873 876 and and CC 877 880 gel gel NN 881 886 shift shift NN 887 893 assays assay NNS 893 894 , , , 895 897 we we PRP 898 902 have have VBP 903 913 identified identify VBN 914 918 four four CD 919 927 distinct distinct JJ 928 935 binding bind VBG 936 941 sites site NNS 942 945 for for IN 946 953 nuclear nuclear JJ 954 962 proteins protein NNS 963 969 within within IN 970 974 this this DT 975 983 positive positive JJ 984 994 regulatory regulatory JJ 995 1002 element element NN 1002 1003 . . . 1004 1008 Site site NN 1009 1010 B B NNP 1011 1012 ( ( ( 1012 1014 nt nt NNS 1015 1019 4519 4519 CD 1020 1022 to to TO 1023 1027 4545 4545 CD 1027 1028 ) ) ) 1029 1041 specifically specifically RB 1042 1047 bound bind VBD 1048 1052 four four CD 1053 1061 distinct distinct JJ 1062 1069 nuclear nuclear JJ 1070 1077 protein protein NN 1078 1087 complexes complex NNS 1087 1088 : : : 1089 1090 a a DT 1091 1101 ubiquitous ubiquitous JJ 1102 1108 factor factor NN 1108 1109 , , , 1110 1111 a a DT 1112 1127 T-cell-specific t-cell-specific JJ 1128 1134 factor factor NN 1134 1135 , , , 1136 1137 a a DT 1138 1153 B-cell-specific b-cell-specific JJ 1154 1160 factor factor NN 1160 1161 , , , 1162 1165 and and CC 1166 1169 the the DT 1170 1190 monocyte/macrophage- monocyte/macrophage- NN 1191 1194 and and CC 1195 1210 B-cell-specific b-cell-specific JJ 1211 1224 transcription transcription NN 1225 1231 factor factor NN 1232 1242 PU.1/Spi-1 pu.1/spi-1 NN 1242 1243 . . . 1244 1246 In in IN 1247 1251 most most JJS 1252 1257 HIV-1 HIV-1 NNP 1258 1266 isolates isolate NNS 1267 1269 in in IN 1270 1275 which which WDT 1276 1280 this this DT 1281 1283 PU PU NNP 1284 1287 box box NN 1288 1291 was be VBD 1292 1295 not not RB 1296 1305 conserved conserve VBN 1305 1306 , , , 1307 1309 it it PRP 1310 1313 was be VBD 1314 1322 replaced replace VBN 1323 1325 by by IN 1326 1327 a a DT 1328 1335 binding bind VBG 1336 1340 site site NN 1341 1344 for for IN 1345 1348 the the DT 1349 1356 related relate VBN 1357 1363 factor factor NN 1364 1368 Ets1 ets1 NN 1368 1369 . . . 1370 1377 Factors factor NNS 1378 1385 binding bind VBG 1386 1388 to to TO 1389 1393 site site NN 1394 1395 C C NNP 1396 1397 ( ( ( 1397 1399 nt nt NNS 1400 1404 4681 4681 CD 1405 1407 to to TO 1408 1412 4701 4701 CD 1412 1413 ) ) ) 1414 1417 had have VBD 1418 1419 a a DT 1420 1431 DNA-binding dna-binding JJ 1432 1443 specificity specificity NN 1444 1451 similar similar JJ 1452 1454 to to TO 1455 1459 that that DT 1460 1462 of of IN 1463 1470 factors factor NNS 1471 1478 binding bind VBG 1479 1481 to to TO 1482 1486 site site NN 1487 1488 B B NNP 1488 1489 , , , 1490 1496 except except IN 1497 1500 for for IN 1501 1511 PU.1/Spi-1 pu.1/spi-1 NN 1511 1512 . . . 1513 1514 A a DT 1515 1517 GC GC NNP 1518 1521 box box NN 1522 1532 containing contain VBG 1533 1534 a a DT 1535 1542 binding bind VBG 1543 1547 site site NN 1548 1551 for for IN 1552 1555 Sp1 Sp1 NNP 1556 1559 was be VBD 1560 1570 identified identify VBN 1571 1572 ( ( ( 1572 1574 nt nt NNS 1575 1579 4623 4623 CD 1580 1582 to to TO 1583 1589 4631). 4631). CD 1590 1594 Site Site NNP 1595 1596 D D NNP 1597 1598 ( ( ( 1598 1600 nt nt NNS 1601 1605 4816 4816 CD 1606 1608 to to TO 1609 1613 4851 4851 CD 1613 1614 ) ) ) 1615 1627 specifically specifically RB 1628 1633 bound bind VBD 1634 1635 a a DT 1636 1648 ubiquitously ubiquitously RB 1649 1658 expressed express VBN 1659 1665 factor factor NN 1665 1666 . . . 1667 1672 These these DT 1673 1680 results result NNS 1681 1689 identify identify VBP 1690 1691 a a DT 1692 1707 transcriptional transcriptional JJ 1708 1718 regulatory regulatory JJ 1719 1726 element element NN 1727 1737 associated associate VBN 1738 1742 with with IN 1743 1744 a a DT 1745 1768 nuclease-hypersensitive nuclease-hypersensitive JJ 1769 1773 site site NN 1774 1776 in in IN 1777 1780 the the DT 1781 1784 pol pol NN 1785 1789 gene gene NN 1790 1792 of of IN 1793 1798 HIV-1 HIV-1 NNP 1799 1802 and and CC 1803 1810 suggest suggest VBP 1811 1815 that that IN 1816 1819 its its PRP$ 1820 1828 activity activity NN 1829 1832 may may MD 1833 1835 be be VB 1836 1846 controlled control VBN 1847 1849 by by IN 1850 1851 a a DT 1852 1859 complex complex JJ 1860 1869 interplay interplay NN 1870 1872 of of IN 1873 1887 cis-regulatory cis-regulatory JJ 1888 1896 elements element NNS 1896 1897 . . .