0 2 Of of IN 3 6 the the DT 7 19 GATA-binding gata-binding JJ 20 28 proteins protein NNS 28 29 , , , 30 34 only only RB 35 41 GATA-4 gata-4 NN 42 53 selectively selectively RB 54 63 regulates regulate VBZ 64 67 the the DT 68 73 human human JJ 74 78 IL-5 il-5 NN 79 83 gene gene NN 84 92 promoter promoter NN 93 95 in in IN 96 100 IL-5 il-5 NN 101 110 producing producing NN 111 116 cells cell NNS 117 122 which which WDT 123 130 express express VBP 131 139 multiple multiple JJ 140 152 GATA-binding gata-binding JJ 153 161 proteins protein NNS 161 162 . . . 164 177 Interleukin-5 Interleukin-5 NNP 178 179 ( ( ( 179 183 IL-5 IL-5 NNP 183 184 ) ) ) 185 187 is be VBZ 188 196 produced produce VBN 197 199 by by IN 200 201 T t NN 202 213 lymphocytes lymphocyte NNS 214 217 and and CC 218 223 known know VBN 224 226 to to TO 227 234 support support VB 235 236 B B NNP 237 241 cell cell NN 242 248 growth growth NN 249 252 and and CC 253 265 eosinophilic eosinophilic JJ 266 281 differentiation differentiation NN 282 284 of of IN 285 288 the the DT 289 299 progenitor progenitor NN 300 305 cells cell NNS 305 306 . . . 307 312 Using use VBG 313 320 ATL-16T atl-16t NN 321 326 cells cell NNS 327 332 which which WDT 333 340 express express VBP 341 345 IL-5 IL-5 NNP 346 350 mRNA mRNA NNP 350 351 , , , 352 354 we we PRP 355 359 have have VBP 360 370 identified identify VBN 371 372 a a DT 373 379 region region NN 379 380 , , , 381 387 within within IN 388 391 the the DT 392 397 human human JJ 398 402 IL-5 il-5 NN 403 407 gene gene NN 408 416 promoter promoter NN 416 417 , , , 418 422 that that WDT 423 432 regulates regulate VBZ 433 437 IL-5 IL-5 NNP 438 442 gene gene NN 443 456 transcription transcription NN 456 457 . . . 458 462 This this DT 463 473 cis-acting cis-acting JJ 474 482 sequence sequence NN 483 491 contains contain VBZ 492 495 the the DT 496 500 core core NN 501 508 binding binding NN 509 514 motif motif NN 514 515 , , , 516 517 ( ( ( 517 530 A/T)GATA(A/G) A/T)GATA(A/G) NNP 530 531 , , , 532 535 for for IN 536 548 GATA-binding gata-binding JJ 549 555 family family NN 556 564 proteins protein NNS 565 568 and and CC 569 573 thus thus RB 574 582 suggests suggest VBZ 583 586 the the DT 587 598 involvement involvement NN 599 601 of of IN 602 607 these these DT 608 614 family family NN 615 622 members member NNS 622 623 . . . 624 626 In in IN 627 631 this this DT 632 638 report report NN 638 639 , , , 640 642 we we PRP 643 651 describe describe VBP 652 655 the the DT 656 663 cloning cloning NN 664 666 of of IN 667 672 human human JJ 673 679 GATA-4 gata-4 NN 680 681 ( ( ( 681 688 hGATA-4 hgata-4 NN 688 689 ) ) ) 690 693 and and CC 694 698 show show VBP 699 703 that that IN 704 711 hGATA-4 hgata-4 NN 712 723 selectively selectively RB 724 733 interacts interact VBZ 734 738 with with IN 739 742 the the DT 743 746 -70 -70 CD 747 751 GATA GATA NNP 752 756 site site NN 757 763 within within IN 764 767 the the DT 768 772 IL-5 IL-5 NNP 773 781 proximal proximal JJ 782 790 promoter promoter NN 791 797 region region NN 797 798 . . . 799 801 By by IN 802 810 promoter promoter NN 811 819 deletion deletion NN 820 823 and and CC 824 832 mutation mutation NN 833 841 analyses analysis NNS 841 842 , , , 843 845 we we PRP 846 857 established establish VBD 858 862 this this DT 863 869 region region NN 870 872 as as IN 873 874 a a DT 875 883 positive positive JJ 884 894 regulatory regulatory JJ 895 902 element element NN 902 903 . . . 904 918 Cotransfection cotransfection NN 919 930 experiments experiment NNS 931 939 revealed reveal VBD 940 944 that that IN 945 949 both both CC 950 957 hGATA-4 hgata-4 NN 958 961 and and CC 962 972 PMA/A23187 pma/a23187 NN 973 984 stimulation stimulation NN 985 988 are be VBP 989 998 necessary necessary JJ 999 1002 for for IN 1003 1006 the the DT 1007 1011 IL-5 IL-5 NNP 1012 1020 promoter promoter NN 1021 1031 activation activation NN 1031 1032 . . . 1033 1036 The the DT 1037 1048 requirement requirement NN 1049 1051 of of IN 1052 1059 another another DT 1060 1070 regulatory regulatory JJ 1071 1078 element element NN 1079 1085 called call VBN 1086 1090 CLE0 CLE0 NNP 1090 1091 , , , 1092 1097 which which WDT 1098 1102 lies lie VBZ 1103 1113 downstream downstream RB 1114 1116 of of IN 1117 1120 the the DT 1121 1124 -70 -70 CD 1125 1129 GATA GATA NNP 1130 1134 site site NN 1134 1135 , , , 1136 1139 was be VBD 1140 1144 also also RB 1145 1157 demonstrated demonstrate VBN 1157 1158 . . . 1159 1166 ATL-16T ATL-16T NNP 1167 1172 cells cell NNS 1173 1180 express express VBP 1181 1185 mRNA mrna NN 1186 1188 of of IN 1189 1194 three three CD 1195 1207 GATA-binding gata-binding JJ 1208 1216 proteins protein NNS 1216 1217 , , , 1218 1225 hGATA-2 hgata-2 NN 1225 1226 , , , 1227 1234 hGATA-3 hgata-3 NN 1235 1238 and and CC 1239 1246 hGATA-4 hgata-4 NN 1246 1247 , , , 1248 1251 and and CC 1252 1256 each each DT 1257 1259 of of IN 1260 1264 them them PRP 1265 1268 has have VBZ 1269 1270 a a DT 1271 1280 potential potential NN 1281 1283 to to TO 1284 1288 bind bind VB 1289 1291 to to TO 1292 1295 the the DT 1296 1305 consensus consensus NN 1306 1307 ( ( ( 1307 1318 A/T)GATA(G/ A/T)GATA(G/ NNP 1319 1320 A A NNP 1320 1321 ) ) ) 1322 1327 motif motif NN 1327 1328 . . . 1329 1336 However however RB 1336 1337 , , , 1338 1343 using use VBG 1344 1351 ATL-16T ATL-16T NNP 1352 1359 nuclear nuclear JJ 1360 1367 extract extract NN 1367 1368 , , , 1369 1371 we we PRP 1372 1384 demonstrated demonstrate VBD 1385 1389 that that IN 1390 1396 GATA-4 gata-4 NN 1397 1399 is be VBZ 1400 1403 the the DT 1404 1408 only only RB 1409 1421 GATA-binding gata-binding JJ 1422 1429 protein protein NN 1430 1434 that that WDT 1435 1440 forms form VBZ 1441 1449 specific specific JJ 1450 1461 DNA-protein dna-protein JJ 1462 1469 complex complex NN 1470 1474 with with IN 1475 1478 the the DT 1479 1482 -70 -70 CD 1483 1487 GATA GATA NNP 1488 1492 site site NN 1492 1493 . . . 1494 1497 The the DT 1498 1513 electrophoretic electrophoretic JJ 1514 1522 mobility mobility NN 1523 1528 shift shift NN 1529 1534 assay assay NN 1535 1539 with with IN 1540 1548 extracts extract NNS 1549 1551 of of IN 1552 1555 COS COS NNP 1556 1561 cells cell NNS 1562 1572 expressing express VBG 1573 1585 GATA-binding gata-binding JJ 1586 1594 proteins protein NNS 1595 1601 showed show VBD 1602 1606 that that IN 1607 1613 GATA-4 gata-4 NN 1614 1617 has have VBZ 1618 1621 the the DT 1622 1629 highest high JJS 1630 1637 binding binding NN 1638 1646 affinity affinity NN 1647 1649 to to TO 1650 1653 the the DT 1654 1657 -70 -70 CD 1658 1662 GATA GATA NNP 1663 1667 site site NN 1668 1673 among among IN 1674 1677 the the DT 1678 1683 three three CD 1684 1696 GATA-binding gata-binding JJ 1697 1705 proteins protein NNS 1705 1706 . . . 1707 1711 When when WRB 1712 1715 the the DT 1716 1731 transactivation transactivation NN 1732 1739 ability ability NN 1740 1743 was be VBD 1744 1752 compared compare VBN 1753 1758 among among IN 1759 1762 the the DT 1763 1768 three three CD 1768 1769 , , , 1770 1776 GATA-4 gata-4 NN 1777 1783 showed show VBD 1784 1787 the the DT 1788 1795 highest high JJS 1796 1804 activity activity NN 1804 1805 . . . 1806 1811 These these DT 1812 1819 results result NNS 1820 1831 demonstrate demonstrate VBP 1832 1835 the the DT 1836 1845 selective selective JJ 1846 1850 role role NN 1851 1853 of of IN 1854 1860 GATA-4 gata-4 NN 1861 1863 in in IN 1864 1867 the the DT 1868 1883 transcriptional transcriptional JJ 1884 1894 regulation regulation NN 1895 1897 of of IN 1898 1901 the the DT 1902 1906 IL-5 il-5 NN 1907 1911 gene gene NN 1912 1914 in in IN 1915 1916 a a DT 1917 1929 circumstance circumstance NN 1930 1935 where where WRB 1936 1944 multiple multiple JJ 1945 1952 members member NNS 1953 1955 of of IN 1956 1959 the the DT 1960 1972 GATA-binding gata-binding JJ 1973 1981 proteins protein NNS 1982 1985 are be VBP 1986 1995 expressed express VBN 1995 1996 . . .