0 2 An an DT 3 12 intricate intricate JJ 13 24 arrangement arrangement NN 25 27 of of IN 28 35 binding bind VBG 36 41 sites site NNS 42 45 for for IN 46 49 the the DT 50 53 Ets Ets NNP 54 60 family family NN 61 63 of of IN 64 77 transcription transcription NN 78 85 factors factor NNS 86 95 regulates regulate VBZ 96 104 activity activity NN 105 107 of of IN 108 111 the the DT 112 117 alpha alpha NN 118 119 4 4 CD 120 128 integrin integrin NN 129 133 gene gene NN 134 143 promoter. promoter. NN 145 150 alpha alpha NN 151 152 4 4 CD 153 162 integrins integrin NNS 163 170 mediate mediate VBP 171 180 cell-cell cell-cell JJ 181 184 and and CC 185 203 cell-extracellular cell-extracellular JJ 204 210 matrix matrix NN 211 223 interactions interaction NNS 224 228 that that WDT 229 232 are be VBP 233 241 critical critical JJ 242 245 for for IN 246 256 maturation maturation NN 257 260 and and CC 261 269 function function NN 270 272 of of IN 273 276 the the DT 277 283 immune immune JJ 284 290 system system NN 291 293 as as RB 294 298 well well RB 299 301 as as IN 302 317 differentiation differentiation NN 318 320 of of IN 321 329 skeletal skeletal JJ 330 336 muscle muscle NN 336 337 . . . 338 342 Here here RB 343 345 we we PRP 346 353 examine examine VBP 354 363 molecular molecular JJ 364 374 mechanisms mechanism NNS 375 386 controlling control VBG 387 390 the the DT 391 398 pattern pattern NN 399 401 of of IN 402 407 alpha alpha NN 408 409 4 4 CD 410 420 expression expression NN 420 421 . . . 422 425 The the DT 426 434 activity activity NN 435 437 of of IN 438 448 constructs construct NNS 449 459 containing contain VBG 460 461 5 5 CD 461 462 ’ ' SYM 463 471 deletion deletion NN 472 479 mutants mutant NNS 480 482 of of IN 483 486 the the DT 487 492 alpha alpha NN 493 494 4 4 CD 495 499 gene gene NN 500 508 promoter promoter NN 509 512 was be VBD 513 521 compared compare VBN 522 524 in in IN 525 537 transfection transfection NN 538 544 assays assay NNS 545 549 into into IN 550 554 cell cell NN 555 560 lines line NNS 561 565 that that WDT 566 573 express express VBP 574 579 alpha alpha NN 580 581 4 4 CD 582 585 and and CC 586 590 cell cell NN 591 596 lines line NNS 597 601 that that WDT 602 604 do do VBP 605 608 not not RB 608 609 . . . 610 613 The the DT 614 622 sequence sequence NN 623 630 between between IN 631 639 position position NN 640 643 -42 -42 CD 644 647 and and CC 648 651 -76 -76 CD 652 656 base base NN 657 662 pairs pair NNS 663 664 ( ( ( 664 666 bp bp NN 666 667 ) ) ) 668 671 was be VBD 672 680 required require VBN 681 684 for for IN 685 694 efficient efficient JJ 695 708 transcription transcription NN 709 711 in in IN 712 717 cells cell NNS 718 722 that that WDT 723 730 express express VBP 731 736 alpha alpha NN 737 738 4 4 CD 738 739 , , , 740 743 but but CC 744 746 it it PRP 747 753 showed show VBD 754 756 no no DT 757 765 activity activity NN 766 768 in in IN 769 773 HeLa HeLa NNP 774 779 cells cell NNS 779 780 , , , 781 786 which which WDT 787 789 do do VBP 790 793 not not RB 794 801 express express VB 802 807 alpha alpha NN 808 809 4 4 CD 809 810 . . . 811 816 Three three CD 817 824 binding bind VBG 825 830 sites site NNS 831 834 for for IN 835 838 the the DT 839 842 Ets Ets NNP 843 849 family family NN 850 852 of of IN 853 866 transcription transcription NN 867 874 factors factor NNS 875 878 are be VBP 879 884 found find VBN 885 887 in in IN 888 892 this this DT 893 899 region region NN 899 900 : : : 901 904 two two CD 905 913 adjacent adjacent JJ 914 919 sites site NNS 920 922 at at IN 923 932 positions position NNS 933 936 -50 -50 CD 937 940 and and CC 941 944 -54 -54 CD 945 947 bp bp NN 948 951 and and CC 952 953 a a DT 954 958 more more JJR 959 960 5 5 CD 960 961 ’ ' SYM 962 966 site site NN 967 969 at at IN 970 978 position position NN 979 982 -67 -67 CD 983 986 bp. bp. NN 987 992 Using use VBG 993 994 a a DT 995 1001 series series NN 1002 1004 of of IN 1005 1015 constructs construct NNS 1016 1026 containing contain VBG 1027 1036 deletions deletion NNS 1037 1040 and and CC 1041 1050 mutations mutation NNS 1051 1053 in in IN 1054 1058 this this DT 1059 1065 region region NN 1065 1066 , , , 1067 1069 we we PRP 1070 1075 found find VBD 1076 1080 that that IN 1081 1084 the the DT 1085 1092 3’-most 3'-most JJ 1093 1097 site site NN 1098 1103 alone alone RB 1104 1107 was be VBD 1108 1118 sufficient sufficient JJ 1119 1122 for for IN 1123 1130 binding bind VBG 1131 1141 GA-binding ga-binding JJ 1142 1149 protein protein NN 1150 1155 alpha alpha NN 1156 1157 ( ( ( 1157 1161 GABP GABP NNP 1162 1173 alpha)/GABP alpha)/GABP NNP 1174 1178 beta beta NN 1179 1182 and and CC 1183 1186 for for IN 1187 1188 a a DT 1189 1192 low low JJ 1193 1198 level level NN 1199 1201 of of IN 1202 1217 transcriptional transcriptional JJ 1218 1228 activation activation NN 1228 1229 . . . 1230 1234 When when WRB 1235 1238 all all DT 1239 1244 three three CD 1245 1250 sites site NNS 1251 1255 were be VBD 1256 1263 present present JJ 1263 1264 , , , 1265 1266 a a DT 1267 1273 second second JJ 1274 1281 complex complex NN 1282 1283 “ `` `` 1283 1284 a a DT 1284 1285 ” '' '' 1286 1289 was be VBD 1290 1298 detected detect VBN 1298 1299 , , , 1300 1305 which which WDT 1306 1314 contains contain VBZ 1315 1317 an an DT 1318 1325 unknown unknown JJ 1326 1332 member member NN 1333 1335 of of IN 1336 1339 the the DT 1340 1343 Ets Ets NNP 1344 1350 family family NN 1350 1351 . . . 1352 1361 Formation formation NN 1362 1364 of of IN 1365 1372 complex complex NN 1373 1374 a a DT 1375 1378 was be VBD 1379 1388 cell-type cell-type JJ 1389 1397 specific specific JJ 1398 1401 and and CC 1402 1412 correlated correlate VBD 1413 1417 with with IN 1418 1419 a a DT 1420 1424 high high JJ 1425 1430 level level NN 1431 1433 of of IN 1434 1447 transcription transcription NN 1447 1448 . . . 1449 1457 Deletion deletion NN 1458 1460 of of IN 1461 1464 the the DT 1465 1472 5’-most 5'-most JJ 1473 1476 Ets ets NN 1477 1481 site site NN 1482 1485 had have VBD 1486 1488 no no DT 1489 1495 effect effect NN 1496 1498 on on IN 1499 1506 binding binding NN 1507 1509 to to TO 1510 1514 GABP GABP NNP 1515 1525 alpha/GABP alpha/GABP NNP 1526 1530 beta beta NN 1530 1531 , , , 1532 1535 but but CC 1536 1538 it it PRP 1539 1549 eliminated eliminate VBD 1550 1552 a. a. RB 1553 1564 Concomitant concomitant JJ 1565 1569 with with IN 1570 1574 this this DT 1575 1579 loss loss NN 1580 1582 of of IN 1583 1584 a a DT 1584 1585 , , , 1586 1587 a a DT 1588 1591 new new JJ 1592 1608 Ets-1-containing ets-1-containing JJ 1609 1616 complex complex NN 1617 1618 “ `` `` 1618 1619 c c NN 1619 1620 ” '' '' 1621 1629 appeared appear VBD 1629 1630 . . . 1631 1638 Complex complex NN 1639 1640 c c NN 1641 1652 substituted substitute VBN 1653 1664 efficiently efficiently RB 1665 1668 for for IN 1669 1676 complex complex NN 1677 1678 a a NN 1679 1681 in in IN 1682 1697 transcriptional transcriptional JJ 1698 1708 activation activation NN 1708 1709 . . . 1710 1712 We we PRP 1713 1721 conclude conclude VBP 1722 1726 that that IN 1727 1735 although although IN 1736 1743 neither neither DT 1744 1746 of of IN 1747 1750 the the DT 1751 1754 two two CD 1755 1762 5’-most 5'-most JJ 1763 1766 Ets ets NN 1767 1772 sites site NNS 1773 1778 alone alone RB 1779 1784 binds bind VBZ 1785 1792 nuclear nuclear JJ 1793 1800 protein protein NN 1800 1801 , , , 1802 1806 they they PRP 1807 1813 appear appear VBP 1814 1816 to to TO 1817 1820 act act VB 1821 1823 as as IN 1824 1834 modulators modulator NNS 1835 1840 which which WDT 1841 1848 control control VBP 1849 1852 the the DT 1853 1860 pattern pattern NN 1861 1863 of of IN 1864 1867 Ets Ets NNP 1868 1876 proteins protein NNS 1877 1881 that that WDT 1882 1886 bind bind VBP 1887 1890 the the DT 1891 1896 alpha alpha NN 1897 1898 4 4 CD 1899 1903 gene gene NN 1904 1912 promoter promoter NN 1912 1913 . . . 1914 1918 This this DT 1919 1930 arrangement arrangement NN 1931 1933 of of IN 1934 1937 Ets Ets NNP 1938 1943 sites site NNS 1943 1944 , , , 1945 1952 coupled couple VBN 1953 1957 with with IN 1958 1961 the the DT 1962 1969 tissue- tissue- NN 1970 1973 and and CC 1974 1996 developmental-specific developmental-specific JJ 1997 2007 expression expression NN 2008 2010 of of IN 2011 2014 Ets Ets NNP 2015 2022 members member NNS 2022 2023 , , , 2024 2030 likely likely RB 2031 2035 play play VBP 2036 2037 a a DT 2038 2041 key key JJ 2042 2046 role role NN 2047 2049 in in IN 2050 2058 defining define VBG 2059 2062 the the DT 2063 2070 pattern pattern NN 2071 2073 of of IN 2074 2079 alpha alpha NN 2080 2081 4 4 CD 2082 2090 integrin integrin NN 2090 2091 . . .