0 8 Targeted target VBN 9 19 remodeling remodeling NN 20 22 of of IN 23 28 human human JJ 29 40 beta-globin beta-globin NN 41 49 promoter promoter NN 50 59 chromatin chromatin NN 60 69 structure structure NN 70 78 produces produce VBZ 79 88 increased increase VBN 89 99 expression expression NN 100 103 and and CC 104 113 decreased decrease VBN 114 123 silencing silencing NN 123 124 . . . 126 129 The the DT 130 139 chromatin chromatin NN 140 149 structure structure NN 150 152 of of IN 153 156 the the DT 157 162 human human JJ 163 174 beta-globin beta-globin NN 175 179 gene gene NN 180 185 locus locus NN 186 193 assumes assume VBZ 194 195 a a DT 196 220 transcriptionally-active transcriptionally-active JJ 221 233 conformation conformation NN 234 236 in in IN 237 246 erythroid erythroid JJ 247 252 cells cell NNS 252 253 . . . 254 257 One one CD 258 265 feature feature NN 266 268 of of IN 269 273 this this DT 274 283 chromatin chromatin NN 284 298 reorganization reorganization NN 299 301 is be VBZ 302 305 the the DT 306 315 formation formation NN 316 318 of of IN 319 324 DNase DNase NNP 325 326 1 1 CD 327 341 hypersensitive hypersensitive JJ 342 347 sites site NNS 348 350 in in IN 351 354 the the DT 355 362 regions region NNS 363 365 of of IN 366 372 active active JJ 373 379 globin globin NN 380 384 gene gene NN 385 394 promoters promoter NNS 394 395 . . . 396 400 This this DT 401 415 reorganization reorganization NN 416 424 requires require VBZ 425 428 the the DT 429 435 globin globin NN 436 441 locus locus NN 442 449 control control NN 450 456 region region NN 457 460 and and CC 461 463 is be VBZ 464 474 associated associate VBN 475 479 with with IN 480 486 normal normal JJ 487 497 expression expression NN 498 500 of of IN 501 504 the the DT 505 514 beta-like beta-like JJ 515 521 globin globin NN 522 527 genes gene NNS 527 528 . . . 529 531 To to TO 532 541 determine determine VB 542 549 whether whether IN 550 552 it it PRP 553 555 is be VBZ 556 564 possible possible JJ 565 567 to to TO 568 580 artificially artificially RB 581 588 enhance enhance VB 589 592 the the DT 593 600 opening opening NN 601 603 of of IN 604 607 the the DT 608 617 chromatin chromatin NN 618 627 structure structure NN 628 630 of of IN 631 632 a a DT 633 640 minimal minimal JJ 641 652 beta-globin beta-globin NN 653 661 promoter promoter NN 661 662 , , , 663 665 we we PRP 666 672 placed place VBD 673 674 a a DT 675 680 101bp 101bp NN 680 681 , , , 682 700 erythroid-specific erythroid-specific JJ 701 706 DNase DNase NNP 707 708 1 1 CD 709 723 hypersensitive hypersensitive JJ 724 736 site-forming site-forming JJ 737 744 element element NN 745 746 ( ( ( 746 750 HSFE HSFE NNP 750 751 ) ) ) 752 763 immediately immediately RB 764 772 upstream upstream JJ 773 775 of of IN 776 779 the the DT 780 791 beta-globin beta-globin NN 792 800 promoter promoter NN 801 804 and and CC 805 809 gene gene NN 809 810 . . . 811 815 This this DT 816 823 element element NN 824 832 includes include VBZ 833 840 binding bind VBG 841 846 sites site NNS 847 850 for for IN 851 856 NF-E2 NF-E2 NNP 856 857 , , , 858 862 AP-1 AP-1 NNP 862 863 , , , 864 870 GATA-1 gata-1 NN 871 874 and and CC 875 879 Sp-1 sp-1 NN 879 880 . . . 881 891 Constructs construct NNS 892 896 were be VBD 897 903 stably stably RB 904 915 transfected transfecte VBN 916 920 into into IN 921 927 murine murine JJ 928 943 erythroleukemia erythroleukemia NN 944 949 cells cell NNS 950 953 and and CC 954 962 promoter promoter NN 963 972 chromatin chromatin NN 973 982 structure structure NN 983 986 and and CC 987 991 gene gene NN 992 1002 expression expression NN 1003 1007 were be VBD 1008 1016 analyzed analyze VBN 1016 1017 . . . 1018 1021 The the DT 1022 1026 HSFE HSFE NNP 1027 1034 induced induce VBD 1035 1037 an an DT 1038 1042 area area NN 1043 1045 of of IN 1046 1054 enhanced enhance VBN 1055 1060 DNase DNase NNP 1061 1062 1 1 CD 1063 1079 hypersensitivity hypersensitivity NN 1080 1089 extending extend VBG 1090 1094 from from IN 1095 1098 the the DT 1099 1114 transcriptional transcriptional JJ 1115 1120 start start NN 1121 1125 site site NN 1126 1128 to to TO 1129 1135 -300bp -300bp NN 1136 1138 of of IN 1139 1142 the the DT 1143 1153 artificial artificial JJ 1154 1162 promoter promoter NN 1163 1166 and and CC 1167 1180 significantly significantly RB 1181 1190 increased increase VBD 1191 1194 the the DT 1195 1205 proportion proportion NN 1206 1208 of of IN 1209 1220 beta-globin beta-globin NN 1221 1230 promoters promoter NNS 1231 1233 in in IN 1234 1236 an an DT 1237 1241 open open JJ 1242 1251 chromatin chromatin NN 1252 1265 configuration configuration NN 1265 1266 . . . 1267 1271 This this DT 1272 1282 remodeling remodeling NN 1283 1285 of of IN 1286 1294 promoter promoter NN 1295 1304 chromatin chromatin NN 1305 1314 structure structure NN 1315 1323 resulted result VBD 1324 1326 in in IN 1327 1333 3-fold 3-fold JJ 1334 1343 increases increase NNS 1344 1346 in in IN 1347 1358 beta-globin beta-globin NN 1359 1363 gene gene NN 1364 1377 transcription transcription NN 1378 1381 and and CC 1382 1391 induction induction NN 1391 1392 , , , 1393 1396 and and CC 1397 1406 inhibited inhibit VBD 1407 1416 long-term long-term JJ 1417 1428 beta-globin beta-globin NN 1429 1433 gene gene NN 1434 1443 silencing silencing NN 1443 1444 . . . 1445 1450 These these DT 1451 1458 results result NNS 1459 1467 indicate indicate VBP 1468 1472 that that IN 1473 1474 a a DT 1475 1485 relatively relatively RB 1486 1491 small small JJ 1492 1502 cis-acting cis-acting JJ 1503 1510 element element NN 1511 1513 is be VBZ 1514 1518 able able JJ 1519 1521 to to TO 1522 1529 enhance enhance VB 1530 1540 remodeling remodeling NN 1541 1543 of of IN 1544 1552 promoter promoter NN 1553 1562 chromatin chromatin NN 1563 1572 structure structure NN 1573 1582 resulting result VBG 1583 1585 in in IN 1586 1595 increased increase VBN 1596 1607 beta-globin beta-globin NN 1608 1612 gene gene NN 1613 1623 expression expression NN 1623 1624 . . .