0 1 A a DT 2 8 factor factor NN 9 14 known know VBN 15 17 to to TO 18 22 bind bind VB 23 25 to to TO 26 36 endogenous endogenous JJ 37 39 Ig Ig NNP 40 45 heavy heavy JJ 46 51 chain chain NN 52 60 enhancer enhancer NN 61 65 only only RB 66 68 in in IN 69 80 lymphocytes lymphocyte NNS 81 83 is be VBZ 84 85 a a DT 86 98 ubiquitously ubiquitously RB 99 105 active active JJ 106 119 transcription transcription NN 120 126 factor factor NN 126 127 . . . 129 132 The the DT 133 148 transcriptional transcriptional JJ 149 157 enhancer enhancer NN 158 165 located located JJ 166 168 in in IN 169 172 the the DT 173 178 first first JJ 179 185 intron intron NN 186 188 of of IN 189 192 the the DT 193 207 immunoglobulin immunoglobulin NN 208 213 heavy heavy JJ 214 219 chain chain NN 220 228 constant constant NN 229 235 region region NN 236 238 is be VBZ 239 240 a a DT 241 246 major major JJ 247 258 determinant determinant NN 259 261 of of IN 262 277 B-cell-specific b-cell-specific JJ 278 288 expression expression NN 289 291 of of IN 292 306 immunoglobulin immunoglobulin NN 307 312 genes gene NNS 312 313 . . . 314 318 Like like IN 319 324 other other JJ 325 334 enhancers enhancer NNS 334 335 , , , 336 339 the the DT 340 342 Ig Ig NNP 343 348 heavy heavy JJ 349 354 chain chain NN 355 363 enhancer enhancer NN 364 372 contains contain VBZ 373 380 several several JJ 381 386 short short JJ 387 395 sequence sequence NN 396 402 motifs motif NNS 403 407 that that WDT 408 412 bind bind VBP 413 421 specific specific JJ 422 435 transcription transcription NN 436 443 factors factor NNS 443 444 . . . 445 449 Each each DT 450 457 binding bind VBG 458 462 site site NN 463 474 contributes contribute VBZ 475 477 to to TO 478 481 the the DT 482 489 overall overall JJ 490 498 activity activity NN 499 501 of of IN 502 505 the the DT 506 514 enhancer enhancer NN 514 515 , , , 516 523 however however RB 524 526 no no DT 527 533 single single JJ 534 541 element element NN 542 547 seems seem VBZ 548 558 absolutely absolutely RB 559 567 required require VBN 568 571 for for IN 572 580 activity activity NN 580 581 . . . 582 585 For for IN 586 587 a a DT 588 594 better good JJR 595 608 understanding understanding NN 609 611 of of IN 612 615 the the DT 616 618 Ig Ig NNP 619 624 heavy heavy JJ 625 630 chain chain NN 631 639 enhancer enhancer NN 640 650 components component NNS 650 651 , , , 652 654 we we PRP 655 659 have have VBP 660 666 cloned clone VBN 667 670 and and CC 671 679 analyzed analyze VBN 680 690 individual individual JJ 691 699 sequence sequence NN 700 708 elements element NNS 708 709 . . . 710 712 We we PRP 713 717 find find VBP 718 722 that that IN 723 726 the the DT 727 733 factor factor NN 734 738 that that WDT 739 744 binds bind VBZ 745 747 to to TO 748 751 the the DT 752 754 E3 e3 NN 755 763 enhancer enhancer NN 764 769 motif motif NN 769 770 , , , 771 779 CATGTGGC CATGTGGC NNP 779 780 , , , 781 783 is be VBZ 784 785 a a DT 786 796 ubiquitous ubiquitous JJ 797 810 transcription transcription NN 811 817 factor factor NN 817 818 . . . 819 821 It it PRP 822 824 is be VBZ 825 832 present present JJ 833 835 in in IN 836 838 an an DT 839 845 active active JJ 846 850 form form NN 851 853 in in IN 854 858 both both CC 859 860 B B NNP 861 866 cells cell NNS 867 870 and and CC 871 876 non-B non-b JJ 877 882 cells cell NNS 882 883 , , , 884 889 where where WRB 890 892 it it PRP 893 896 can can MD 897 904 mediate mediate VB 905 920 transcriptional transcriptional JJ 921 931 activation activation NN 932 934 in in FW 935 940 vitro vitro FW 941 944 and and CC 945 947 in in FW 948 952 vivo vivo FW 952 953 . . . 954 961 However however RB 961 962 , , , 963 970 despite despite IN 971 974 its its PRP$ 975 982 ability ability NN 983 985 to to TO 986 994 activate activate VB 995 1008 transcription transcription NN 1009 1011 of of IN 1012 1013 a a DT 1014 1025 transfected transfecte VBN 1026 1034 reporter reporter NN 1035 1039 gene gene NN 1039 1040 , , , 1041 1044 the the DT 1045 1051 factor factor NN 1052 1054 is be VBZ 1055 1065 apparently apparently RB 1066 1072 unable unable JJ 1073 1075 to to TO 1076 1080 bind bind VB 1081 1083 to to TO 1084 1087 the the DT 1088 1098 endogenous endogenous JJ 1099 1101 Ig Ig NNP 1102 1107 heavy heavy JJ 1108 1113 chain chain NN 1114 1122 enhancer enhancer NN 1123 1125 in in IN 1126 1138 non-lymphoid non-lymphoid JJ 1139 1144 cells cell NNS 1144 1145 : : : 1146 1148 In in IN 1149 1157 previous previous JJ 1158 1169 experiments experiment NNS 1170 1172 by by IN 1173 1179 others other NNS 1179 1180 , , , 1181 1184 the the DT 1185 1199 characteristic characteristic JJ 1200 1202 in in FW 1203 1207 vivo vivo FW 1208 1217 footprint footprint NN 1218 1220 of of IN 1221 1225 this this DT 1226 1232 factor factor NN 1232 1233 , , , 1234 1244 designated designate VBN 1245 1252 NF-muE3 NF-muE3 NNP 1252 1253 , , , 1254 1257 was be VBD 1258 1266 detected detect VBN 1267 1269 in in IN 1270 1271 B B NNP 1272 1277 cells cell NNS 1278 1281 but but CC 1282 1285 not not RB 1286 1288 in in IN 1289 1294 non-B non-b JJ 1295 1300 cells cell NNS 1300 1301 . . . 1302 1306 From from IN 1307 1311 this this DT 1312 1315 and and CC 1316 1321 other other JJ 1322 1330 findings finding NNS 1331 1334 the the DT 1335 1342 picture picture NN 1343 1350 emerges emerge VBZ 1351 1355 that that IN 1356 1361 there there EX 1362 1365 are be VBP 1366 1368 at at IN 1369 1374 least least JJS 1375 1380 three three CD 1381 1391 categories category NNS 1392 1394 of of IN 1395 1402 factors factor NNS 1403 1408 which which WDT 1409 1416 mediate mediate VBP 1417 1435 cell-type-specific cell-type-specific JJ 1436 1449 transcription transcription NN 1450 1452 in in IN 1453 1454 B B NNP 1455 1466 lymphocytes lymphocyte NNS 1466 1467 : : : 1468 1469 ( ( ( 1469 1470 a a LS 1470 1471 ) ) ) 1472 1485 cell-specific cell-specific JJ 1486 1493 factors factor NNS 1494 1498 such such JJ 1499 1501 as as IN 1502 1508 Oct-2A Oct-2A NNP 1509 1512 and and CC 1513 1519 Oct-2B Oct-2B NNP 1520 1524 that that WDT 1525 1528 are be VBP 1529 1532 not not RB 1533 1542 expressed express VBN 1543 1545 in in IN 1546 1550 most most JJS 1551 1556 other other JJ 1557 1561 cell cell NN 1562 1567 types type NNS 1567 1568 : : : 1569 1570 ( ( ( 1570 1571 b b LS 1571 1572 ) ) ) 1573 1583 ubiquitous ubiquitous JJ 1584 1591 factors factor NNS 1592 1596 such such JJ 1597 1599 as as IN 1600 1608 NF-kappa NF-kappa NNP 1609 1610 B B NNP 1611 1615 that that WDT 1616 1619 are be VBP 1620 1634 constitutively constitutively RB 1635 1641 active active JJ 1642 1644 in in IN 1645 1646 B B NNP 1647 1652 cells cell NNS 1653 1656 but but CC 1657 1660 are be VBP 1661 1672 sequestered sequester VBN 1673 1675 in in IN 1676 1678 an an DT 1679 1687 inactive inactive JJ 1688 1692 form form NN 1693 1695 in in IN 1696 1701 other other JJ 1702 1707 cells cell NNS 1707 1708 ; ; : 1709 1710 ( ( ( 1710 1711 c c LS 1711 1712 ) ) ) 1713 1725 ubiquitously ubiquitously RB 1726 1732 active active JJ 1733 1740 factors factor NNS 1740 1741 , , , 1742 1753 exemplified exemplify VBN 1754 1756 by by IN 1757 1760 the the DT 1761 1764 one one CD 1765 1772 binding binding NN 1773 1775 to to TO 1776 1779 the the DT 1780 1782 E3 e3 NN 1783 1791 sequence sequence NN 1792 1797 motif motif NN 1797 1798 . . . 1799 1803 This this DT 1804 1810 factor factor NN 1811 1813 is be VBZ 1814 1821 present present JJ 1822 1824 in in IN 1825 1827 an an DT 1828 1834 active active JJ 1835 1839 form form NN 1840 1842 in in IN 1843 1844 a a DT 1845 1852 variety variety NN 1853 1855 of of IN 1856 1860 cell cell NN 1861 1866 types type NNS 1867 1870 but but CC 1871 1873 is be VBZ 1874 1884 apparently apparently RB 1885 1891 unable unable JJ 1892 1894 to to TO 1895 1899 bind bind VB 1900 1902 to to TO 1903 1906 the the DT 1907 1917 endogenous endogenous JJ 1918 1920 Ig Ig NNP 1921 1926 heavy heavy JJ 1927 1932 chain chain NN 1933 1941 enhancer enhancer NN 1942 1944 in in IN 1945 1950 non-B non-b JJ 1951 1956 cells cell NNS 1956 1957 , , , 1958 1965 perhaps perhaps RB 1966 1969 due due JJ 1970 1972 to to TO 1973 1974 a a DT 1975 1989 non-permissive non-permissive JJ 1990 1999 chromatin chromatin NN 2000 2009 structure structure NN 2010 2012 of of IN 2013 2016 the the DT 2017 2019 Ig Ig NNP 2020 2025 heavy heavy JJ 2026 2031 chain chain NN 2032 2037 locus locus NN 2037 2038 . . .