0 1 T t NN 2 15 cell-specific cell-specific JJ 16 24 negative negative JJ 25 35 regulation regulation NN 36 38 of of IN 39 52 transcription transcription NN 53 55 of of IN 56 59 the the DT 60 65 human human JJ 66 74 cytokine cytokine NN 75 79 IL-4 il-4 NN 79 80 . . . 82 86 IL-4 il-4 NN 87 95 secreted secrete VBN 96 98 by by IN 99 108 activated activate VBN 109 110 T t NN 111 116 cells cell NNS 117 119 is be VBZ 120 121 a a DT 122 133 pleiotropic pleiotropic JJ 134 142 cytokine cytokine NN 143 152 affecting affect VBG 153 159 growth growth NN 160 163 and and CC 164 179 differentiation differentiation NN 180 182 of of IN 183 190 diverse diverse JJ 191 195 cell cell NN 196 201 types type NNS 202 206 such such JJ 207 209 as as IN 210 211 T t NN 212 217 cells cell NNS 217 218 , , , 219 220 B B NNP 221 226 cells cell NNS 226 227 , , , 228 231 and and CC 232 236 mast mast NN 237 242 cells cell NNS 242 243 . . . 244 246 We we PRP 247 259 investigated investigate VBD 260 263 the the DT 264 272 upstream upstream JJ 273 283 regulatory regulatory JJ 284 292 elements element NNS 293 295 of of IN 296 299 the the DT 300 305 human human JJ 306 310 IL-4 il-4 NN 311 319 promoter promoter NN 319 320 . . . 321 322 A a DT 323 328 novel novel JJ 329 330 T t NN 331 344 cell-specific cell-specific JJ 345 353 negative negative JJ 354 364 regulatory regulatory JJ 365 372 element element NN 373 374 ( ( ( 374 377 NRE NRE NNP 377 378 ) ) ) 379 387 composed compose VBN 388 390 of of IN 391 394 two two CD 395 410 protein-binding protein-binding JJ 411 416 sites site NNS 417 421 were be VBD 422 428 mapped map VBN 429 431 in in IN 432 435 the the DT 436 437 5 5 CD 437 438 ’ ' SYM 439 447 flanking flanking NN 448 454 region region NN 455 457 of of IN 458 461 the the DT 462 466 IL-4 il-4 NN 467 471 gene gene NN 471 472 : : : 473 490 -311CTCCCTTCT-303 -311CTCCCTTCT-303 NNP 491 492 ( ( ( 492 497 NRE-I NRE-I NNP 497 498 ) ) ) 499 502 and and CC 503 525 -288CTTTTTGCTT-TGC-300 -288CTTTTTGCTT-TGC-300 NNP 526 527 ( ( ( 527 533 NRE-II NRE-II NNP 533 534 ) ) ) 534 535 . . . 536 537 A a DT 538 539 T t NN 540 553 cell-specific cell-specific JJ 554 561 protein protein NN 562 567 Neg-1 neg-1 NN 568 571 and and CC 572 573 a a DT 574 584 ubiquitous ubiquitous JJ 585 592 protein protein NN 593 598 Neg-2 neg-2 NN 599 606 binding bind VBG 607 609 to to TO 610 615 NRE-I NRE-I NNP 616 619 and and CC 620 626 NRE-II NRE-II NNP 626 627 , , , 628 640 respectively respectively RB 640 641 , , , 642 646 were be VBD 647 657 identified identify VBN 657 658 . . . 659 670 Furthermore furthermore RB 670 671 , , , 672 673 a a DT 674 682 positive positive JJ 683 693 regulatory regulatory JJ 694 701 element element NN 702 705 was be VBD 706 711 found find VBN 712 714 45 45 CD 715 717 bp bp NN 718 728 downstream downstream RB 729 731 of of IN 732 735 the the DT 736 739 NRE nre NN 739 740 . . . 741 744 The the DT 745 753 enhancer enhancer NN 754 762 activity activity NN 763 765 of of IN 766 769 the the DT 770 773 PRE pre NN 774 777 was be VBD 778 788 completely completely RB 789 799 suppressed suppress VBN 800 804 when when WRB 805 808 the the DT 809 812 NRE nre NN 813 816 was be VBD 817 824 present present JJ 824 825 . . . 826 831 These these DT 832 836 data datum NNS 837 844 suggest suggest VBP 845 849 that that IN 850 854 IL-4 il-4 NN 855 863 promoter promoter NN 864 872 activity activity NN 873 875 is be VBZ 876 884 normally normally RB 885 899 down-regulated down-regulate VBN 900 902 by by IN 903 905 an an DT 906 909 NRE nre NN 910 913 via via IN 914 924 repression repression NN 925 927 of of IN 928 931 the the DT 932 940 enhancer enhancer NN 941 949 positive positive JJ 950 960 regulatory regulatory JJ 961 968 element element NN 968 969 . . . 970 975 These these DT 976 980 data datum NNS 981 984 may may MD 985 989 have have VB 990 1002 implications implication NNS 1003 1006 for for IN 1007 1010 the the DT 1011 1020 stringent stringent JJ 1021 1028 control control NN 1029 1031 of of IN 1032 1036 IL-4 il-4 NN 1037 1047 expression expression NN 1048 1050 in in IN 1051 1052 T t NN 1053 1058 cells cell NNS 1058 1059 . . .