0 15 Tissue-specific tissue-specific JJ 16 24 activity activity NN 25 27 of of IN 28 31 the the DT 32 38 gammac gammac NN 39 44 chain chain NN 45 49 gene gene NN 50 58 promoter promoter NN 59 66 depends depend VBZ 67 71 upon upon IN 72 74 an an DT 75 78 Ets Ets NNP 79 86 binding binding NN 87 91 site site NN 92 95 and and CC 96 98 is be VBZ 99 108 regulated regulate VBN 109 111 by by IN 112 122 GA-binding ga-binding JJ 123 130 protein protein NN 130 131 . . . 133 136 The the DT 137 143 gammac gammac NN 144 149 chain chain NN 150 152 is be VBZ 153 154 a a DT 155 162 subunit subunit NN 163 165 of of IN 166 174 multiple multiple JJ 175 183 cytokine cytokine NN 184 193 receptors receptor NNS 194 195 ( ( ( 195 206 interleukin interleukin NN 207 208 ( ( ( 208 213 IL)-2 IL)-2 NNP 213 214 , , , 215 219 IL-4 il-4 NN 219 220 , , , 221 225 IL-7 IL-7 NNP 225 226 , , , 227 231 IL-9 IL-9 NNP 231 232 , , , 233 236 and and CC 237 242 IL-15 IL-15 NNP 242 243 ) ) ) 243 244 , , , 245 248 the the DT 249 259 expression expression NN 260 262 of of IN 263 268 which which WDT 269 271 is be VBZ 272 282 restricted restricted JJ 283 285 to to TO 286 299 hematopoietic hematopoietic JJ 300 308 lineages lineage NNS 308 309 . . . 310 311 A a DT 312 318 defect defect NN 319 321 in in IN 322 328 gammac gammac NN 329 334 leads lead VBZ 335 337 to to TO 338 341 the the DT 342 350 X-linked x-linked JJ 351 357 severe severe JJ 358 366 combined combined JJ 367 383 immunodeficiency immunodeficiency NN 384 397 characterized characterize VBN 398 400 by by IN 401 402 a a DT 403 408 block block NN 409 411 in in IN 412 413 T t NN 414 418 cell cell NN 419 434 differentiation differentiation NN 434 435 . . . 436 438 In in IN 439 444 order order NN 445 447 to to TO 448 454 better well RBR 455 467 characterize characterize VB 468 471 the the DT 472 477 human human JJ 478 484 gammac gammac NN 485 493 promoter promoter NN 494 497 and and CC 498 504 define define VB 505 508 the the DT 509 516 minimal minimal JJ 517 532 tissue-specific tissue-specific JJ 533 541 promoter promoter NN 542 548 region region NN 548 549 , , , 550 561 progressive progressive JJ 562 573 5’-deletion 5'-deletion JJ 574 584 constructs construct NNS 585 587 of of IN 588 589 a a DT 590 597 segment segment NN 598 607 extending extend VBG 608 612 1053 1053 CD 613 617 base base NN 618 623 pairs pair NNS 624 632 upstream upstream RB 633 635 of of IN 636 639 the the DT 640 645 major major JJ 646 659 transcription transcription NN 660 665 start start NN 666 670 site site NN 671 675 were be VBD 676 685 generated generate VBN 686 689 and and CC 690 696 tested test VBN 697 700 for for IN 701 709 promoter promoter NN 710 718 activity activity NN 719 721 in in IN 722 729 various various JJ 730 743 hematopoietic hematopoietic JJ 744 747 and and CC 748 764 nonhematopoietic nonhematopoietic JJ 765 769 cell cell NN 770 775 types type NNS 775 776 . . . 777 780 The the DT 781 790 -1053/+34 -1053/+34 CD 791 800 construct construct NN 801 808 allowed allow VBD 809 817 promoter promoter NN 818 826 activity activity NN 827 831 only only RB 832 834 in in IN 835 840 cells cell NNS 841 843 of of IN 844 857 hematopoietic hematopoietic JJ 858 864 origin origin NN 864 865 , , , 866 869 and and CC 870 876 tissue tissue NN 877 888 specificity specificity NN 889 892 was be VBD 893 902 conserved conserve VBN 903 905 in in IN 906 909 all all DT 910 915 other other JJ 916 926 constructs construct NNS 927 933 tested test VBN 933 934 . . . 935 938 The the DT 939 945 region region NN 946 956 downstream downstream JJ 957 959 of of IN 960 963 -90 -90 CD 964 972 appeared appear VBD 973 981 critical critical JJ 982 985 for for IN 986 991 basal basal JJ 992 1000 promoter promoter NN 1001 1009 activity activity NN 1009 1010 . . . 1011 1013 It it PRP 1014 1022 contains contain VBZ 1023 1026 two two CD 1027 1036 potential potential JJ 1037 1040 Ets ets NN 1041 1048 binding binding NN 1049 1054 sites site NNS 1055 1064 conserved conserve VBN 1065 1067 in in IN 1068 1071 the the DT 1072 1078 murine murine JJ 1079 1085 gammac gammac NN 1086 1094 promoter promoter NN 1095 1099 gene gene NN 1099 1100 , , , 1101 1104 one one CD 1105 1107 of of IN 1108 1113 which which WDT 1114 1117 was be VBD 1118 1123 found find VBN 1124 1133 essential essential JJ 1134 1137 for for IN 1138 1148 functional functional JJ 1149 1157 promoter promoter NN 1158 1166 activity activity NN 1167 1169 as as IN 1170 1180 determined determine VBN 1181 1183 by by IN 1184 1194 mutational mutational JJ 1195 1203 analysis analysis NN 1203 1204 . . . 1205 1208 The the DT 1209 1219 functional functional JJ 1220 1223 Ets ets NN 1224 1231 binding binding NN 1232 1236 site site NN 1237 1240 was be VBD 1241 1246 found find VBN 1247 1249 to to TO 1250 1254 bind bind VB 1255 1258 Ets ets NN 1259 1265 family family NN 1266 1274 proteins protein NNS 1274 1275 , , , 1276 1287 principally principally RB 1288 1298 GA-binding ga-binding JJ 1299 1306 protein protein NN 1307 1310 and and CC 1311 1316 Elf-1 elf-1 NN 1317 1320 and and CC 1321 1326 could could MD 1327 1329 be be VB 1330 1344 transactivated transactivate VBN 1345 1347 by by IN 1348 1357 GABPalpha GABPalpha NNP 1358 1361 and and CC 1362 1367 -beta -beta NN 1368 1383 synergistically synergistically RB 1383 1384 . . . 1385 1390 These these DT 1391 1398 results result NNS 1399 1407 indicate indicate VBP 1408 1412 that that IN 1412 1413 , , , 1414 1416 as as IN 1417 1424 already already RB 1425 1433 reported report VBN 1434 1437 for for IN 1438 1441 the the DT 1442 1450 IL2Rbeta IL2Rbeta NNP 1451 1459 promoter promoter NN 1459 1460 , , , 1461 1471 GA-binding ga-binding JJ 1472 1479 protein protein NN 1480 1482 is be VBZ 1483 1485 an an DT 1486 1495 essential essential JJ 1496 1505 component component NN 1506 1508 of of IN 1509 1515 gammac gammac NN 1516 1521 basal basal JJ 1522 1530 promoter promoter NN 1531 1539 activity activity NN 1539 1540 . . . 1541 1549 Although although IN 1550 1554 GABP GABP NNP 1555 1565 expression expression NN 1566 1568 is be VBZ 1569 1572 not not RB 1573 1583 restricted restricted JJ 1584 1586 to to TO 1587 1590 the the DT 1591 1604 hematopoietic hematopoietic JJ 1605 1612 lineage lineage NN 1612 1613 , , , 1614 1617 its its PRP$ 1618 1629 interaction interaction NN 1630 1634 with with IN 1635 1640 other other JJ 1641 1649 specific specific JJ 1650 1657 factors factor NNS 1658 1661 may may MD 1662 1672 contribute contribute VB 1673 1675 to to TO 1676 1679 the the DT 1680 1695 tissue-specific tissue-specific JJ 1696 1706 expression expression NN 1707 1709 of of IN 1710 1713 the the DT 1714 1720 gammac gammac NN 1721 1725 gene gene NN 1725 1726 . . .