0 7 Binding binding NN 8 10 of of IN 11 20 erythroid erythroid JJ 21 24 and and CC 25 38 non-erythroid non-erythroid JJ 39 46 nuclear nuclear JJ 47 55 proteins protein NNS 56 58 to to TO 59 62 the the DT 63 71 silencer silencer NN 72 74 of of IN 75 78 the the DT 79 84 human human JJ 85 108 epsilon-globin-encoding epsilon-globin-encoding JJ 109 113 gene gene NN 113 114 . . . 116 118 To to TO 119 126 clarify clarify VB 127 130 the the DT 131 140 molecular molecular JJ 141 151 mechanisms mechanism NNS 152 160 involved involve VBN 161 163 in in IN 164 167 the the DT 168 181 developmental developmental JJ 182 189 control control NN 190 192 of of IN 193 212 hemoglobin-encoding hemoglobin-encoding JJ 213 218 genes gene NNS 219 221 we we PRP 222 226 have have VBP 227 231 been be VBN 232 240 studying study VBG 241 244 the the DT 245 255 expression expression NN 256 258 of of IN 259 264 these these DT 265 270 genes gene NNS 271 273 in in IN 274 279 human human JJ 280 285 cells cell NNS 286 288 in in IN 289 299 continuous continuous JJ 300 307 culture culture NN 307 308 . . . 309 311 We we PRP 312 316 have have VBP 317 327 previously previously RB 328 336 reported report VBN 337 340 the the DT 341 349 presence presence NN 350 352 of of IN 353 354 a a DT 355 370 transcriptional transcriptional JJ 371 378 control control NN 379 386 element element NN 387 391 with with IN 392 395 the the DT 396 406 properties property NNS 407 409 of of IN 410 411 a a DT 412 420 silencer silencer NN 421 430 extending extend VBG 431 435 from from IN 436 440 -392 -392 CD 441 443 to to TO 444 448 -177 -177 CD 449 451 bp bp NN 452 460 relative relative JJ 461 463 to to TO 464 467 the the DT 468 471 cap cap NN 472 476 site site NN 477 479 of of IN 480 483 the the DT 484 489 human human JJ 490 513 epsilon-globin-encoding epsilon-globin-encoding JJ 514 518 gene gene NN 519 520 [ [ ( 520 523 Cao Cao NNP 524 526 et et FW 527 530 al. al. FW 530 531 , , , 532 554 Proc.Natl.Acad.Sci.USA Proc.Natl.Acad.Sci.USA NNP 555 557 86 86 CD 558 559 ( ( ( 559 563 1989 1989 CD 563 564 ) ) ) 565 574 5306-5309 5306-5309 CD 574 575 ] ] ) 575 576 . . . 577 579 We we PRP 580 584 also also RB 585 591 showed show VBD 592 596 that that IN 597 601 this this DT 602 610 silencer silencer NN 611 614 has have VBZ 615 623 stronger strong JJR 624 634 inhibitory inhibitory JJ 635 643 activity activity NN 644 646 in in IN 647 651 HeLa HeLa NNP 652 657 cells cell NNS 657 658 , , , 659 661 as as IN 662 670 compared compare VBN 671 673 to to TO 674 678 K562 k562 NN 679 684 human human JJ 685 700 erythroleukemia erythroleukemia NN 701 706 cells cell NNS 706 707 . . . 708 713 Using use VBG 714 722 deletion deletion NN 723 730 mutants mutant NNS 731 734 and and CC 735 745 cis-cloned cis-cloned JJ 746 755 synthetic synthetic JJ 756 781 oligodeoxyribonucleotides oligodeoxyribonucleotide NNS 782 784 in in IN 785 794 transient transient JJ 795 805 expression expression NN 806 812 assays assay NNS 812 813 , , , 814 824 nucleotide nucleotide NN 825 834 sequences sequence NNS 835 846 responsible responsible JJ 847 850 for for IN 851 855 this this DT 856 862 effect effect NN 863 867 have have VBP 868 871 now now RB 872 876 been be VBN 877 884 further further RBR 885 894 delimited delimit VBN 895 897 to to TO 898 900 44 44 CD 901 903 bp bp NN 904 911 located located JJ 912 916 from from IN 917 921 -294 -294 CD 922 924 to to TO 925 929 -251 -251 CD 930 933 bp. bp. NN 934 937 Gel Gel NNP 938 953 electrophoresis electrophoresis NN 954 962 mobility mobility NN 963 968 shift shift NN 969 975 assays assay NNS 976 979 and and CC 980 986 DNaseI DNaseI NNP 987 999 footprinting footprinting NN 1000 1006 assays assay NNS 1007 1018 demonstrate demonstrate VBP 1019 1023 that that IN 1024 1029 these these DT 1030 1038 negative negative JJ 1039 1049 regulatory regulatory JJ 1050 1059 sequences sequence NNS 1060 1063 are be VBP 1064 1074 recognized recognize VBN 1075 1086 differently differently RB 1087 1089 by by IN 1090 1098 proteins protein NNS 1099 1106 present present JJ 1107 1109 in in IN 1110 1117 nuclear nuclear JJ 1118 1126 extracts extract NNS 1127 1135 obtained obtain VBN 1136 1140 from from IN 1141 1145 HeLa HeLa NNP 1146 1149 and and CC 1150 1154 K562 k562 NN 1155 1160 cells cell NNS 1160 1161 . . . 1162 1165 Two two CD 1166 1173 binding bind VBG 1174 1182 proteins protein NNS 1183 1186 are be VBP 1187 1195 detected detect VBN 1196 1198 in in IN 1199 1203 K562 k562 NN 1204 1211 nuclear nuclear JJ 1212 1220 extracts extract NNS 1220 1221 , , , 1222 1227 while while IN 1228 1232 only only RB 1233 1236 one one CD 1237 1239 is be VBZ 1240 1245 found find VBN 1246 1248 in in IN 1249 1257 extracts extract NNS 1258 1262 from from IN 1263 1267 HeLa HeLa NNP 1268 1273 cells cell NNS 1273 1274 . . . 1275 1283 Possible possible JJ 1284 1294 mechanisms mechanism NNS 1295 1297 by by IN 1298 1303 which which WDT 1304 1309 these these DT 1310 1318 proteins protein NNS 1319 1322 may may MD 1323 1331 regulate regulate VB 1332 1345 transcription transcription NN 1346 1348 of of IN 1349 1352 the the DT 1353 1376 epsilon-globin-encoding epsilon-globin-encoding JJ 1377 1381 gene gene NN 1382 1384 in in IN 1385 1394 erythroid erythroid JJ 1395 1398 and and CC 1399 1412 non-erythroid non-erythroid JJ 1413 1418 cells cell NNS 1419 1422 are be VBP 1423 1432 discussed discuss VBN 1432 1433 . . .