0 3 One one CD 4 8 base base NN 9 13 pair pair NN 14 20 change change NN 21 30 abolishes abolish VBZ 31 34 the the DT 35 36 T t NN 37 52 cell-restricted cell-restricted JJ 53 61 activity activity NN 62 64 of of IN 65 66 a a DT 67 74 kB-like kb-like JJ 75 89 proto-enhancer proto-enhancer NN 90 97 element element NN 98 102 from from IN 103 106 the the DT 107 118 interleukin interleukin NN 119 120 2 2 CD 121 129 promoter promoter NN 129 130 . . . 132 135 The the DT 136 145 inducible inducible JJ 145 146 , , , 147 148 T t NN 149 162 cell-specific cell-specific JJ 163 172 enhancers enhancer NNS 173 175 of of IN 176 182 murine murine JJ 183 186 and and CC 187 192 human human JJ 193 204 Interleukin Interleukin NNP 205 206 2 2 CD 207 208 ( ( ( 208 212 Il-2 il-2 NN 212 213 ) ) ) 214 219 genes gene NNS 220 227 contain contain VBP 228 231 the the DT 232 239 kB-like kb-like JJ 240 248 sequence sequence NN 249 260 GGGATTTCACC GGGATTTCACC NNP 261 263 as as IN 264 266 an an DT 267 276 essential essential JJ 277 287 cis-acting cis-acting JJ 288 296 enhancer enhancer NN 297 302 motif motif NN 302 303 . . . 304 308 When when WRB 309 315 cloned clone VBN 316 318 in in IN 319 327 multiple multiple JJ 328 334 copies copy NNS 335 339 this this DT 340 349 so-called so-called JJ 350 354 TCEd TCEd NNP 355 356 ( ( ( 356 362 distal distal JJ 363 364 T t NN 365 369 cell cell NN 370 377 element element NN 377 378 ) ) ) 379 383 acts act VBZ 384 386 as as IN 387 389 an an DT 390 399 inducible inducible JJ 400 414 proto-enhancer proto-enhancer NN 415 422 element element NN 423 425 in in IN 426 429 E14 e14 NN 430 431 T t NN 432 440 lymphoma lymphoma NN 441 446 cells cell NNS 446 447 , , , 448 451 but but CC 452 455 not not RB 456 458 in in IN 459 463 HeLa HeLa NNP 464 469 cells cell NNS 469 470 . . . 471 473 In in IN 474 482 extracts extract NNS 483 485 of of IN 486 493 induced induce VBN 493 494 , , , 495 499 Il-2 il-2 NN 500 509 secreting secreting NN 510 513 El4 el4 NN 514 519 cells cell NNS 520 525 three three CD 526 536 individual individual JJ 537 544 protein protein NN 545 552 factors factor NNS 553 557 bind bind VBP 558 560 to to TO 561 565 TCEd TCEd NNP 566 569 DNA DNA NNP 569 570 . . . 571 574 The the DT 575 582 binding binding NN 583 585 of of IN 586 589 the the DT 590 594 most most RBS 595 604 prominent prominent JJ 605 611 factor factor NN 611 612 , , , 613 618 named name VBN 619 624 TCF-1 tcf-1 NN 625 626 ( ( ( 626 627 T t NN 628 632 cell cell NN 633 639 factor factor NN 640 641 1 1 CD 641 642 ) ) ) 642 643 , , , 644 646 is be VBZ 647 657 correlated correlate VBN 658 662 with with IN 663 666 the the DT 667 681 proto-enhancer proto-enhancer NN 682 690 activity activity NN 691 693 of of IN 694 698 TCEd TCEd NNP 698 699 . . . 700 705 TCF-1 TCF-1 NNP 706 714 consists consist VBZ 715 717 of of IN 718 721 two two CD 722 734 polypeptides polypeptide NNS 735 737 of of IN 738 743 about about IN 744 746 50 50 CD 747 749 kD kd NN 750 753 and and CC 754 757 105 105 CD 758 760 kD kd NN 760 761 ; ; : 762 765 the the DT 766 772 former former JJ 773 778 seems seem VBZ 779 781 to to TO 782 784 be be VB 785 792 related related JJ 793 795 to to TO 796 799 the the DT 800 802 50 50 CD 803 805 kD kd NN 806 817 polypeptide polypeptide NN 818 820 of of IN 821 826 NF-kB NF-kB NNP 826 827 . . . 828 836 Purified purify VBN 837 842 NF-kB NF-kB NNP 843 845 is be VBZ 846 850 also also RB 851 855 able able JJ 856 858 to to TO 859 863 bind bind VB 864 866 to to TO 867 870 the the DT 871 875 TCEd TCEd NNP 875 876 , , , 877 880 but but CC 881 886 TCF-1 tcf-1 NN 887 892 binds bind VBZ 893 901 stronger strong JJR 902 906 than than IN 907 912 NF-kB NF-kB NNP 913 915 to to TO 916 920 TCEd TCEd NNP 921 924 DNA DNA NNP 924 925 . . . 926 929 The the DT 930 940 conversion conversion NN 941 943 of of IN 944 947 the the DT 948 952 TCEd tced NN 953 955 to to TO 956 957 a a DT 958 959 ‘ ` `` 959 966 perfect perfect JJ 966 967 ’ ' '' 968 973 NF-kB NF-kB NNP 974 981 binding binding NN 982 986 site site NN 987 992 leads lead VBZ 993 995 to to TO 996 997 a a DT 998 1005 tighter tight JJR 1006 1013 binding binding NN 1014 1016 of of IN 1017 1022 NF-kB NF-kB NNP 1023 1025 to to TO 1026 1030 TCEd TCEd NNP 1031 1034 DNA DNA NNP 1035 1038 and and CC 1038 1039 , , , 1040 1042 as as IN 1043 1044 a a DT 1045 1055 functional functional JJ 1056 1067 consequence consequence NN 1067 1068 , , , 1069 1071 to to TO 1072 1075 the the DT 1076 1084 activity activity NN 1085 1087 of of IN 1088 1091 the the DT 1092 1093 ‘ ` `` 1093 1102 converted convert VBN 1102 1103 ’ ' '' 1104 1108 TCEd tced NN 1109 1115 motifs motif NNS 1116 1118 in in IN 1119 1123 HeLa HeLa NNP 1124 1129 cells cell NNS 1129 1130 . . . 1131 1135 Thus thus RB 1135 1136 , , , 1137 1140 the the DT 1141 1153 substitution substitution NN 1154 1156 of of IN 1157 1160 the the DT 1161 1171 underlined underline VBN 1172 1173 A a NN 1174 1181 residue residue NN 1182 1184 to to TO 1185 1186 a a DT 1187 1188 C C NNP 1189 1195 within within IN 1196 1199 the the DT 1200 1211 GGGATTTCACC GGGATTTCACC NNP 1212 1217 motif motif NN 1218 1227 abolishes abolish VBZ 1228 1231 its its PRP$ 1232 1233 T t NN 1234 1249 cell-restricted cell-restricted JJ 1250 1258 activity activity NN 1259 1262 and and CC 1263 1268 leads lead VBZ 1269 1271 to to TO 1272 1275 its its PRP$ 1276 1287 functioning functioning NN 1288 1290 in in IN 1291 1295 both both DT 1296 1299 El4 el4 NN 1300 1305 cells cell NNS 1306 1309 and and CC 1310 1314 HeLa HeLa NNP 1315 1320 cells cell NNS 1320 1321 . . . 1322 1327 These these DT 1328 1335 results result NNS 1336 1344 indicate indicate VBP 1345 1349 that that IN 1350 1369 lymphocyte-specific lymphocyte-specific JJ 1370 1377 factors factor NNS 1378 1385 binding bind VBG 1386 1388 to to TO 1389 1392 the the DT 1393 1397 TCEd TCEd NNP 1398 1401 are be VBP 1402 1410 involved involve VBN 1411 1413 in in IN 1414 1417 the the DT 1418 1425 control control NN 1426 1428 of of IN 1429 1430 T t NN 1431 1435 cell cell NN 1436 1458 specific-transcription specific-transcription NN 1459 1461 of of IN 1462 1465 the the DT 1466 1470 Il-2 il-2 NN 1471 1475 gene gene NN 1475 1476 . . .