0 7 Nuclear nuclear JJ 8 18 factor-IL6 factor-il6 NN 19 28 activates activate VBZ 29 32 the the DT 33 38 human human JJ 39 43 IL-4 il-4 NN 44 52 promoter promoter NN 53 55 in in IN 56 57 T t NN 58 63 cells cell NNS 63 64 . . . 66 74 Positive positive JJ 75 85 regulatory regulatory JJ 86 93 element element NN 94 95 I i CD 96 97 ( ( ( 97 102 PRE-I PRE-I NNP 102 103 ) ) ) 104 106 is be VBZ 107 108 a a DT 109 115 strong strong JJ 116 124 enhancer enhancer NN 125 132 element element NN 133 142 essential essential JJ 143 146 for for IN 147 157 expression expression NN 158 160 of of IN 161 164 the the DT 165 170 human human JJ 171 175 IL-4 il-4 NN 176 180 gene gene NN 180 181 . . . 182 184 To to TO 185 193 identify identify VB 194 207 transcription transcription NN 208 215 factors factor NNS 216 223 binding bind VBG 224 226 to to TO 227 232 PRE-I PRE-I NNP 232 233 , , , 234 236 we we PRP 237 245 screened screen VBD 246 247 a a DT 248 252 cDNA cdna NN 253 263 expression expression NN 264 271 library library NN 272 276 from from IN 277 283 Jurkat Jurkat NNP 284 285 T t NN 286 291 cells cell NNS 292 295 and and CC 296 304 isolated isolate VBD 305 306 a a DT 307 311 cDNA cdna NN 312 320 encoding encode VBG 321 328 nuclear nuclear JJ 329 335 factor factor NN 336 337 ( ( ( 337 344 NF)-IL6 NF)-IL6 NNP 345 346 ( ( ( 346 350 also also RB 351 356 known know VBN 357 359 as as IN 360 365 C/EBP C/EBP NNP 366 370 beta beta NN 370 371 ) ) ) 371 372 . . . 373 379 NF-IL6 NF-IL6 NNP 380 384 mRNA mRNA NNP 385 388 was be VBD 389 394 found find VBN 395 397 in in IN 398 403 human human JJ 404 410 Jurkat Jurkat NNP 411 412 T t NN 413 418 cells cell NNS 419 422 and and CC 423 425 in in IN 426 429 the the DT 430 435 mouse mouse NN 436 439 Th2 th2 NN 440 445 clone clone NN 446 449 D10 d10 NN 449 450 , , , 451 454 but but CC 455 458 not not RB 459 461 in in IN 462 465 Th1 th1 NN 466 471 clone clone NN 472 475 29. 29. CD 476 483 rNF-IL6 rnf-il6 NN 484 493 expressed express VBN 494 496 in in IN 497 505 bacteria bacteria NNS 506 509 was be VBD 510 515 shown show VBN 516 518 to to TO 519 531 specifically specifically RB 532 536 bind bind VB 537 539 to to TO 540 545 PRE-I PRE-I NNP 545 546 . . . 547 552 PRE-I PRE-I NNP 553 558 forms form VBZ 559 567 multiple multiple JJ 568 579 DNA-protein dna-protein JJ 580 589 complexes complex NNS 590 594 with with IN 595 602 nuclear nuclear JJ 603 611 extracts extract NNS 612 616 from from IN 617 623 Jurkat Jurkat NNP 624 629 cells cell NNS 629 630 . . . 631 635 Some some DT 636 638 of of IN 639 644 these these DT 645 654 complexes complex NNS 655 659 were be VBD 660 672 demonstrated demonstrate VBN 673 675 to to TO 676 683 contain contain VB 684 690 NF-IL6 nf-il6 NN 691 693 by by IN 694 699 using use VBG 700 710 anti-C/EBP anti-c/ebp JJ 711 715 beta beta NN 716 719 Abs ab NNS 719 720 . . . 721 735 Overexpression Overexpression NNP 736 738 of of IN 739 745 NF-IL6 NF-IL6 NNP 746 754 enhanced enhance VBD 755 765 expression expression NN 766 768 of of IN 769 772 the the DT 773 788 chloramphenicol chloramphenicol NN 789 795 acetyl acetyl NN 796 807 transferase transferase NN 808 816 reporter reporter NN 817 821 gene gene NN 822 828 linked link VBN 829 831 to to TO 832 835 the the DT 836 851 PRE-I-thymidine PRE-I-thymidine NNP 852 858 kinase kinase NNP 859 861 or or CC 862 865 the the DT 866 871 human human JJ 872 876 IL-4 il-4 NN 877 885 promoter promoter NN 886 890 more more RBR 891 895 than than IN 896 903 10-fold 10-fold RB 904 906 in in IN 907 913 Jurkat Jurkat NNP 914 919 cells cell NNS 919 920 . . . 921 929 Promoter promoter NN 930 938 deletion deletion NN 939 946 studies study NNS 947 955 revealed reveal VBD 956 959 two two CD 960 970 additional additional JJ 971 977 NF-IL6 nf-il6 NN 978 985 binding binding NN 986 991 sites site NNS 992 999 located located JJ 1000 1002 at at IN 1003 1012 positions position NNS 1013 1016 -44 -44 CD 1017 1019 to to TO 1020 1023 -36 -36 CD 1024 1025 ( ( ( 1025 1030 C/EBP C/EBP NNP 1031 1039 proximal proximal NN 1039 1040 ) ) ) 1041 1044 and and CC 1045 1048 -87 -87 CD 1049 1051 to to TO 1052 1055 -79 -79 CD 1056 1057 ( ( ( 1057 1062 C/EBP C/EBP NNP 1063 1069 medial medial NN 1069 1070 ) ) ) 1070 1071 , , , 1072 1084 respectively respectively RB 1084 1085 . . . 1086 1089 Our our PRP$ 1090 1097 results result NNS 1098 1109 demonstrate demonstrate VBP 1110 1114 that that IN 1115 1121 NF-IL6 NF-IL6 NNP 1122 1124 is be VBZ 1125 1133 involved involve VBN 1134 1136 in in IN 1137 1152 transcriptional transcriptional JJ 1153 1163 activation activation NN 1164 1166 of of IN 1167 1170 the the DT 1171 1176 human human JJ 1177 1181 IL-4 il-4 NN 1182 1190 promoter promoter NN 1191 1193 in in IN 1194 1195 T t NN 1196 1201 cells cell NNS 1201 1202 . . .