0 6 T-cell t-cell NN 7 17 expression expression NN 18 20 of of IN 21 24 the the DT 25 30 human human JJ 31 37 GATA-3 gata-3 NN 38 42 gene gene NN 43 45 is be VBZ 46 55 regulated regulate VBN 56 58 by by IN 59 60 a a DT 61 81 non-lineage-specific non-lineage-specific JJ 82 90 silencer silencer NN 90 91 . . . 93 96 The the DT 97 103 GATA-3 gata-3 NN 104 117 transcription transcription NN 118 124 factor factor NN 125 127 is be VBZ 128 136 required require VBN 137 140 for for IN 141 152 development development NN 153 155 of of IN 156 159 the the DT 160 166 T-cell t-cell NN 167 174 lineage lineage NN 175 178 and and CC 179 182 Th2 th2 NN 183 191 cytokine cytokine NN 192 196 gene gene NN 197 207 expression expression NN 208 210 in in IN 211 214 CD4 CD4 NNP 215 222 T-cells T-cell NNP 222 223 . . . 224 226 We we PRP 227 231 have have VBP 232 238 mapped map VBN 239 242 the the DT 243 265 DNase-I-hypersensitive dnase-i-hypersensitive JJ 266 267 ( ( ( 267 269 HS HS NNP 269 270 ) ) ) 271 278 regions region NNS 279 281 of of IN 282 285 the the DT 286 291 human human JJ 292 298 GATA-3 gata-3 NN 299 303 gene gene NN 304 306 in in IN 307 314 T-cells t-cell NNS 315 318 and and CC 319 330 non-T-cells non-t-cell NNS 331 334 and and CC 335 342 studied study VBN 343 348 their their PRP$ 349 364 transcriptional transcriptional JJ 365 375 activities activity NNS 375 376 . . . 377 379 HS HS NNP 380 385 I-III i-iii CD 385 386 , , , 387 394 located located JJ 395 396 5 5 CD 396 397 ’ ' SYM 398 402 from from IN 403 406 the the DT 407 422 transcriptional transcriptional JJ 423 433 initiation initiation NN 434 438 site site NN 438 439 , , , 440 444 were be VBD 445 450 found find VBN 451 453 in in IN 454 467 hematopoietic hematopoietic JJ 468 471 and and CC 472 489 non-hematopoietic non-hematopoietic JJ 490 495 cells cell NNS 495 496 , , , 497 504 whereas whereas IN 505 507 HS HS NNP 508 514 IV-VII iv-vii CD 514 515 , , , 516 523 located located JJ 524 525 3 3 CD 525 526 ’ ' SYM 527 531 from from IN 532 535 the the DT 536 551 transcriptional transcriptional JJ 552 557 start start NN 558 562 site site NN 562 563 , , , 564 568 were be VBD 569 580 exclusively exclusively RB 581 589 observed observe VBN 590 592 in in IN 593 600 T-cells T-cell NNP 600 601 . . . 602 607 Among among IN 608 613 these these DT 614 628 hypersensitive hypersensitive JJ 629 634 sites site NNS 634 635 , , , 636 639 two two CD 640 655 transcriptional transcriptional JJ 656 663 control control NN 664 672 elements element NNS 673 677 were be VBD 678 683 found find VBN 683 684 , , , 685 688 one one CD 689 691 in in IN 692 695 the the DT 696 701 first first JJ 702 708 intron intron NN 709 711 of of IN 712 715 the the DT 716 722 GATA-3 gata-3 NN 723 727 gene gene NN 728 731 and and CC 732 735 the the DT 736 741 other other JJ 742 749 between between IN 750 753 8.3 8.3 CD 754 757 and and CC 758 761 5.9 5.9 CD 762 771 kilobases kilobas NNS 772 773 5 5 CD 773 774 ’ ' SYM 775 779 from from IN 780 783 the the DT 784 790 GATA-3 gata-3 NN 791 806 transcriptional transcriptional JJ 807 817 initiation initiation NN 818 822 site site NN 822 823 . . . 824 827 The the DT 828 833 first first JJ 834 840 intron intron NN 841 846 acted act VBD 847 849 as as IN 850 851 a a DT 852 858 strong strong JJ 859 874 transcriptional transcriptional JJ 875 884 activator activator NN 885 887 in in IN 888 889 a a DT 890 908 position-dependent position-dependent JJ 909 915 manner manner NN 916 919 and and CC 920 924 with with IN 925 927 no no DT 928 937 cell-type cell-type JJ 938 949 specificity specificity NN 949 950 . . . 951 954 The the DT 955 963 upstream upstream JJ 964 974 regulatory regulatory JJ 975 982 element element NN 983 988 could could MD 989 995 confer confer VB 996 1002 T-cell t-cell NN 1003 1014 specificity specificity NN 1015 1017 to to TO 1018 1021 the the DT 1022 1028 GATA-3 gata-3 NN 1029 1037 promoter promoter NN 1038 1046 activity activity NN 1046 1047 , , , 1048 1051 and and CC 1052 1060 analysis analysis NN 1061 1063 of of IN 1064 1068 this this DT 1069 1075 region region NN 1076 1084 revealed reveal VBD 1085 1086 a a DT 1087 1095 707-base 707-base JJ 1096 1100 pair pair NN 1101 1109 silencer silencer NN 1110 1114 that that WDT 1115 1126 drastically drastically RB 1127 1136 inhibited inhibit VBD 1137 1143 GATA-3 gata-3 NN 1144 1152 promoter promoter NN 1153 1161 activity activity NN 1162 1164 in in IN 1165 1176 non-T-cells non-t-cell NNS 1176 1177 . . . 1178 1181 Two two CD 1182 1188 CAGGTG CAGGTG NNP 1189 1196 E-boxes E-box NNPS 1196 1197 , , , 1198 1205 located located JJ 1206 1208 at at IN 1209 1212 the the DT 1213 1216 5’- 5'- CD 1217 1220 and and CC 1221 1228 3’-ends 3'-end NNS 1229 1231 of of IN 1232 1235 the the DT 1236 1244 silencer silencer NN 1244 1245 , , , 1246 1250 were be VBD 1251 1260 necessary necessary JJ 1261 1264 for for IN 1265 1269 this this DT 1270 1278 silencer silencer NN 1279 1287 activity activity NN 1287 1288 . . . 1289 1292 The the DT 1293 1302 3’-CAGGTG 3'-CAGGTG NNP 1303 1308 E-box E-box NNP 1309 1314 could could MD 1315 1319 bind bind VB 1320 1323 USF USF NNP 1324 1332 proteins protein NNS 1332 1333 , , , 1334 1337 the the DT 1338 1348 ubiquitous ubiquitous JJ 1349 1358 repressor repressor NN 1359 1362 ZEB zeb NN 1362 1363 , , , 1364 1366 or or CC 1367 1370 the the DT 1371 1376 basic basic JJ 1377 1393 helix-loop-helix helix-loop-helix JJ 1394 1402 proteins protein NNS 1403 1406 E2A E2A NNP 1407 1410 and and CC 1411 1414 HEB HEB NNP 1414 1415 , , , 1416 1419 and and CC 1420 1422 we we PRP 1423 1429 showed show VBD 1430 1434 that that IN 1435 1436 a a DT 1437 1448 competition competition NN 1449 1456 between between IN 1457 1460 ZEB ZEB NNP 1461 1464 and and CC 1465 1472 E2A/HEB E2A/HEB NNP 1473 1481 proteins protein NNS 1482 1484 is be VBZ 1485 1493 involved involve VBN 1494 1496 in in IN 1497 1500 the the DT 1501 1509 silencer silencer NN 1510 1518 activity activity NN 1518 1519 . . .