0 6 Tandem tandem JJ 7 19 AP-1-binding ap-1-binding JJ 20 25 sites site NNS 26 32 within within IN 33 36 the the DT 37 42 human human JJ 43 54 beta-globin beta-globin NN 55 63 dominant dominant JJ 64 71 control control NN 72 78 region region NN 79 87 function function NN 88 90 as as IN 91 93 an an DT 94 103 inducible inducible JJ 104 112 enhancer enhancer NN 113 115 in in IN 116 125 erythroid erythroid JJ 126 131 cells cell NNS 131 132 . . . 134 135 A a DT 136 144 powerful powerful JJ 145 153 enhancer enhancer NN 154 157 has have VBZ 158 162 been be VBN 163 169 mapped map VBN 170 172 to to TO 173 175 an an DT 176 181 18-bp 18-bp JJ 182 185 DNA dna NN 186 193 segment segment NN 194 201 located located JJ 202 204 11 11 CD 205 207 kb kb NN 208 209 5 5 CD 209 210 ’ ' SYM 211 213 to to TO 214 217 the the DT 218 223 human human JJ 224 238 epsilon-globin epsilon-globin NN 239 243 gene gene NN 244 250 within within IN 251 254 the the DT 255 263 dominant dominant JJ 264 271 control control NN 272 274 or or CC 275 291 locus-activating locus-activating JJ 292 298 region region NN 298 299 . . . 300 304 This this DT 305 313 enhancer enhancer NN 314 316 is be VBZ 317 326 inducible inducible JJ 327 329 in in IN 330 334 K562 k562 NN 335 340 human human JJ 341 356 erythroleukemia erythroleukemia NN 357 362 cells cell NNS 362 363 , , , 364 374 increasing increase VBG 375 381 linked link VBN 382 394 gamma-globin gamma-globin NN 395 414 promoter/luciferase promoter/luciferase NN 415 419 gene gene NN 420 430 expression expression NN 431 433 to to TO 434 442 170-fold 170-fold RB 443 447 over over IN 448 450 an an DT 451 463 enhancerless enhancerless JJ 464 473 construct construct NN 473 474 . . . 475 478 The the DT 479 487 enhancer enhancer NN 488 496 consists consist VBZ 497 499 of of IN 500 506 tandem tandem JJ 507 519 AP-1-binding ap-1-binding JJ 520 525 sites site NNS 525 526 , , , 527 533 phased phase VBD 534 536 10 10 CD 537 539 bp bp NN 540 545 apart apart RB 545 546 , , , 547 552 which which WDT 553 556 are be VBP 557 561 both both DT 562 570 required require VBN 571 574 for for IN 575 579 full full JJ 580 588 activity activity NN 588 589 . . . 590 601 DNA-protein dna-protein JJ 602 609 binding binding NN 610 616 assays assay NNS 617 621 with with IN 622 629 nuclear nuclear JJ 630 638 extracts extract NNS 639 643 from from IN 644 651 induced induce VBN 652 657 cells cell NNS 658 669 demonstrate demonstrate VBP 670 671 a a DT 672 676 high high JJ 677 686 molecular molecular JJ 687 693 weight weight NN 694 701 complex complex NN 702 704 on on IN 705 708 the the DT 709 717 enhancer enhancer NN 717 718 . . . 719 722 The the DT 723 732 formation formation NN 733 735 of of IN 736 740 this this DT 741 748 complex complex NN 749 753 also also RB 754 762 requires require VBZ 763 767 both both CC 768 772 AP-1 ap-1 NN 773 778 sites site NNS 779 782 and and CC 783 793 correlates correlate VBZ 794 798 with with IN 799 806 maximal maximal JJ 807 815 enhancer enhancer NN 816 824 activity activity NN 824 825 . . . 826 835 Induction Induction NNP 836 838 of of IN 839 842 the the DT 843 851 enhancer enhancer NN 852 855 may may MD 856 860 have have VB 861 862 a a DT 863 867 role role NN 868 870 in in IN 871 874 the the DT 875 883 increase increase NN 884 886 in in IN 887 893 globin globin NN 894 898 gene gene NN 899 912 transcription transcription NN 913 917 that that WDT 918 931 characterizes characterize VBZ 932 941 erythroid erythroid JJ 942 952 maturation maturation NN 952 953 . . . 954 962 Enhancer Enhancer NNP 963 971 activity activity NN 972 979 appears appear VBZ 980 982 to to TO 983 985 be be VB 986 994 mediated mediate VBN 995 997 by by IN 998 1001 the the DT 1002 1009 binding binding NN 1010 1012 of of IN 1013 1014 a a DT 1015 1022 complex complex NN 1023 1025 of of IN 1026 1034 proteins protein NNS 1035 1039 from from IN 1040 1043 the the DT 1044 1047 jun jun NN 1048 1051 and and CC 1052 1055 fos fos NN 1056 1064 families family NNS 1065 1067 to to TO 1068 1074 tandem tandem JJ 1075 1079 AP-1 ap-1 NN 1080 1089 consensus consensus NN 1090 1099 sequences sequence NNS 1099 1100 . . .