0 6 Globin Globin NNP 7 11 gene gene NN 12 21 switching switching NN 21 22 . . . 23 25 In in FW 26 30 vivo vivo FW 31 42 protein-DNA protein-dna JJ 43 55 interactions interaction NNS 56 58 of of IN 59 62 the the DT 63 68 human human JJ 69 80 beta-globin beta-globin NN 81 86 locus locus NN 87 89 in in IN 90 99 erythroid erythroid JJ 100 105 cells cell NNS 106 116 expressing express VBG 117 120 the the DT 121 126 fetal fetal JJ 127 129 or or CC 130 133 the the DT 134 139 adult adult JJ 140 146 globin globin NN 147 151 gene gene NN 152 159 program program NN 159 160 . . . 162 164 To to TO 165 177 characterize characterize VB 178 181 the the DT 182 193 protein-DNA protein-dna JJ 194 206 interactions interaction NNS 207 216 important important JJ 217 220 for for IN 221 224 the the DT 225 238 developmental developmental JJ 239 246 control control NN 247 249 of of IN 250 253 the the DT 254 259 human human JJ 260 271 beta-globin beta-globin NN 272 277 locus locus NN 277 278 , , , 279 281 we we PRP 282 290 analyzed analyze VBD 291 293 by by IN 294 296 in in FW 297 301 vivo vivo FW 302 310 dimethyl dimethyl NN 311 318 sulfate sulfate NN 319 331 footprinting footprinting NN 332 341 erythroid erythroid JJ 342 347 cells cell NNS 348 358 expressing express VBG 359 365 either either CC 366 369 the the DT 370 375 fetal fetal JJ 376 378 or or CC 379 382 the the DT 383 388 adult adult JJ 389 395 globin globin NN 396 409 developmental developmental JJ 410 417 program program NN 417 418 . . . 419 421 In in IN 422 425 the the DT 426 431 locus locus NN 432 439 control control NN 440 446 region region NN 447 448 ( ( ( 448 451 LCR LCR NNP 451 452 ) ) ) 453 455 of of IN 456 459 the the DT 460 471 beta-globin beta-globin NN 472 477 locus locus NN 477 478 , , , 479 481 in in FW 482 486 vivo vivo FW 487 497 footprints footprint NNS 498 500 on on IN 501 506 NF-E2 nf-e2 NN 507 508 ( ( ( 508 510 or or CC 511 515 AP-1 ap-1 NN 515 516 ) ) ) 517 520 and and CC 521 527 GATA-1 gata-1 NN 528 534 motifs motif NNS 535 543 remained remain VBD 544 547 the the DT 548 552 same same JJ 553 563 regardless regardless RB 564 566 of of IN 567 574 whether whether IN 575 578 the the DT 579 584 fetal fetal JJ 585 587 or or CC 588 591 the the DT 592 597 adult adult JJ 598 604 globin globin NN 605 610 genes gene NNS 611 614 are be VBP 615 624 expressed express VBN 624 625 . . . 626 628 In in IN 629 637 contrast contrast NN 637 638 , , , 639 641 in in FW 642 646 vivo vivo FW 647 657 footprints footprint NNS 658 660 on on IN 661 663 GT GT NNP 664 665 ( ( ( 665 670 CACCC CACCC NNP 670 671 ) ) ) 672 678 motifs motif NNS 679 687 differed differ VBD 688 695 between between IN 696 699 the the DT 700 705 cells cell NNS 706 716 expressing express VBG 717 720 the the DT 721 726 fetal fetal JJ 727 729 or or CC 730 733 the the DT 734 739 adult adult JJ 740 746 globin globin NN 747 754 program program NN 754 755 . . . 756 758 In in IN 759 767 promoter promoter NN 768 775 regions region NNS 775 776 , , , 777 780 the the DT 781 789 actively actively RB 790 801 transcribed transcribe VBN 802 807 genes gene NNS 808 820 demonstrated demonstrate VBD 821 830 extensive extensive JJ 831 834 and and CC 835 845 consistent consistent JJ 846 856 footprints footprint NNS 857 861 over over IN 862 865 the the DT 866 875 canonical canonical JJ 876 884 elements element NNS 884 885 , , , 886 890 such such JJ 891 893 as as IN 894 899 CACCC CACCC NNP 900 903 and and CC 904 909 CCAAT CCAAT NNP 910 916 motifs motif NNS 916 917 . . . 918 921 The the DT 922 927 adult adult JJ 928 934 globin globin NN 935 945 expressing expressing NN 946 951 cells cell NNS 952 961 displayed display VBD 962 966 more more RBR 967 976 extensive extensive JJ 977 987 footprints footprint NNS 988 992 than than IN 993 996 the the DT 997 1002 fetal fetal JJ 1003 1009 globin globin NN 1010 1020 expressing expressing NN 1021 1026 cells cell NNS 1027 1029 in in IN 1030 1033 the the DT 1034 1035 3 3 CD 1035 1036 ’ ' SYM 1037 1047 regulatory regulatory JJ 1048 1057 sequences sequence NNS 1058 1060 of of IN 1061 1065 both both CC 1066 1069 the the DT 1070 1077 Agamma- agamma- NN 1078 1081 and and CC 1082 1085 the the DT 1086 1097 beta-globin beta-globin NN 1098 1103 genes gene NNS 1103 1104 , , , 1105 1115 suggesting suggest VBG 1116 1117 a a DT 1118 1122 role role NN 1123 1125 of of IN 1126 1131 these these DT 1132 1133 3 3 CD 1133 1134 ’ ' SYM 1135 1143 elements element NNS 1144 1146 in in IN 1147 1158 beta-globin beta-globin NN 1159 1163 gene gene NN 1164 1174 expression expression NN 1174 1175 . . . 1176 1179 Our our PRP$ 1180 1187 results result NNS 1188 1195 suggest suggest VBP 1196 1200 that that IN 1201 1204 the the DT 1205 1209 bulk bulk NN 1210 1212 of of IN 1213 1224 protein-DNA protein-dna JJ 1225 1237 interactions interaction NNS 1238 1242 that that WDT 1243 1252 underlies underlie VBZ 1253 1256 the the DT 1257 1270 developmental developmental JJ 1271 1278 control control NN 1279 1281 of of IN 1282 1288 globin globin NN 1289 1294 genes gene NNS 1295 1300 takes take VBZ 1301 1306 place place NN 1307 1309 in in IN 1310 1313 the the DT 1314 1320 gamma- gamma- NN 1321 1324 and and CC 1325 1336 beta-globin beta-globin NN 1337 1341 gene gene NN 1342 1351 promoters promoter NNS 1351 1352 , , , 1353 1356 and and CC 1357 1361 that that IN 1362 1364 GT gt NN 1365 1371 motifs motif NNS 1372 1374 of of IN 1375 1378 the the DT 1379 1390 beta-globin beta-globin NN 1391 1396 locus locus NN 1397 1400 LCR LCR NNP 1401 1404 may may MD 1405 1409 play play VB 1410 1411 a a DT 1412 1416 role role NN 1417 1419 in in IN 1420 1423 the the DT 1424 1437 developmental developmental JJ 1438 1448 regulation regulation NN 1449 1451 of of IN 1452 1457 human human JJ 1458 1469 beta-globin beta-globin NN 1470 1474 gene gene NN 1475 1485 expression expression NN 1485 1486 , , , 1487 1494 perhaps perhaps RB 1495 1497 by by IN 1498 1508 increasing increase VBG 1509 1512 the the DT 1513 1524 probability probability NN 1525 1527 of of IN 1528 1539 interaction interaction NN 1540 1542 of of IN 1543 1546 the the DT 1547 1550 LCR LCR NNP 1551 1562 holocomplex holocomplex NN 1563 1567 with with IN 1568 1571 the the DT 1572 1577 fetal fetal JJ 1578 1580 or or CC 1581 1584 the the DT 1585 1590 adult adult JJ 1591 1597 globin globin NN 1598 1602 gene gene NN 1602 1603 . . .