0 1 A a DT 2 6 cell cell NN 7 20 type-specific type-specific JJ 21 29 enhancer enhancer NN 30 32 in in IN 33 36 the the DT 37 42 human human JJ 43 47 B7.1 b7.1 NN 48 52 gene gene NN 53 62 regulated regulate VBN 63 65 by by IN 66 75 NF-kappaB NF-kappaB NNP 75 76 . . . 78 81 The the DT 82 95 costimulatory costimulatory JJ 96 104 molecule molecule NN 105 109 B7.1 b7.1 NN 110 118 provides provide VBZ 119 120 a a DT 121 127 second second JJ 128 134 signal signal NN 135 143 critical critical JJ 144 147 for for IN 148 149 T t NN 150 154 cell cell NN 155 165 activation activation NN 165 166 . . . 167 170 The the DT 171 183 distribution distribution NN 184 186 of of IN 187 191 this this DT 192 200 integral integral JJ 201 209 membrane membrane NN 210 217 protein protein NN 218 220 is be VBZ 221 231 restricted restricted JJ 232 234 to to TO 235 242 certain certain JJ 243 250 tissues tissue NNS 251 256 where where WRB 257 260 its its PRP$ 261 266 level level NN 267 269 of of IN 270 280 expression expression NN 281 283 is be VBZ 284 293 modulated modulate VBN 294 296 by by IN 297 305 multiple multiple JJ 306 315 exogenous exogenous JJ 316 323 stimuli stimulus NNS 323 324 . . . 325 327 To to TO 328 336 identify identify VB 337 340 the the DT 341 350 molecular molecular JJ 351 356 basis basis NN 357 360 for for IN 361 372 specificity specificity NN 373 376 and and CC 377 389 inducibility inducibility NN 389 390 , , , 391 394 the the DT 395 404 chromatin chromatin NN 405 418 configuration configuration NN 419 421 of of IN 422 425 the the DT 426 431 human human JJ 432 436 B7.1 b7.1 NN 437 441 gene gene NN 442 445 was be VBD 446 454 examined examine VBN 455 457 in in IN 458 464 intact intact JJ 465 471 nuclei nucleus NNS 472 476 from from IN 477 484 various various JJ 485 489 cell cell NN 490 495 types type NNS 495 496 . . . 497 500 The the DT 501 515 identification identification NN 516 518 of of IN 519 520 a a DT 521 536 tissue-specific tissue-specific JJ 537 554 deoxyribonuclease deoxyribonuclease NN 555 556 I i CD 557 571 hypersensitive hypersensitive JJ 572 576 site site NN 577 590 approximately approximately RB 591 594 3kb 3kb JJ 595 603 upstream upstream RB 604 606 of of IN 607 610 the the DT 611 624 transcription transcription NN 625 630 start start NN 631 635 site site NN 636 639 led lead VBD 640 642 to to TO 643 646 the the DT 647 663 characterization characterization NN 664 666 of of IN 667 668 a a DT 669 673 cell cell NN 674 687 type-specific type-specific JJ 688 696 enhancer enhancer NN 697 703 region region NN 703 704 . . . 705 709 This this DT 710 716 183-bp 183-bp JJ 717 723 region region NN 724 727 was be VBD 728 732 both both CC 733 737 cell cell NN 738 742 type type NN 743 751 specific specific JJ 752 755 and and CC 756 766 responsive responsive JJ 767 769 to to TO 770 773 two two CD 774 782 distinct distinct JJ 783 790 stimuli stimulus NNS 790 791 , , , 792 810 lipopolysaccharide lipopolysaccharide NN 811 814 and and CC 815 824 dibutyryl dibutyryl NN 825 829 cAMP camp NN 829 830 , , , 831 836 known know VBN 837 839 to to TO 840 848 regulate regulate VB 849 853 B7.1 b7.1 NN 854 864 expression expression NN 864 865 . . . 866 876 Deletional deletional JJ 877 880 and and CC 881 894 site-directed site-directed JJ 895 906 mutagenesis mutagenesis NN 907 915 revealed reveal VBD 916 919 the the DT 920 928 presence presence NN 929 931 of of IN 932 940 multiple multiple JJ 941 953 functionally functionally RB 954 962 critical critical JJ 963 966 cis cis NN 967 975 elements element NNS 976 982 within within IN 983 987 this this DT 988 994 region region NN 994 995 , , , 996 999 one one CD 1000 1002 of of IN 1003 1008 which which WDT 1009 1012 was be VBD 1013 1014 a a DT 1015 1022 nuclear nuclear JJ 1023 1029 factor factor NN 1030 1031 ( ( ( 1031 1041 NF)-kappaB NF)-kappaB NNP 1042 1051 consensus consensus NN 1052 1060 sequence sequence NN 1060 1061 . . . 1062 1064 In in IN 1065 1078 B7.1-positive b7.1-positive JJ 1079 1080 B B NNP 1081 1086 cells cell NNS 1086 1087 , , , 1088 1092 this this DT 1093 1100 element element NN 1101 1106 bound bind VBD 1107 1114 several several JJ 1115 1122 members member NNS 1123 1125 of of IN 1126 1129 the the DT 1130 1139 NF-kappaB NF-kappaB NNP 1140 1146 family family NN 1146 1147 , , , 1148 1161 transcription transcription NN 1162 1169 factors factor NNS 1170 1177 already already RB 1178 1188 implicated implicate VBN 1189 1191 in in IN 1192 1198 signal signal NN 1199 1211 transduction transduction NN 1212 1220 pathways pathway NNS 1221 1229 relevant relevant JJ 1230 1232 to to TO 1233 1237 B7.1 b7.1 NN 1238 1248 expression expression NN 1248 1249 . . . 1250 1254 This this DT 1255 1257 is be VBZ 1258 1261 the the DT 1262 1267 first first JJ 1268 1279 description description NN 1279 1280 , , , 1281 1283 to to TO 1284 1287 our our PRP$ 1288 1297 knowledge knowledge NN 1297 1298 , , , 1299 1301 of of IN 1302 1312 regulatory regulatory JJ 1313 1321 elements element NNS 1322 1326 that that WDT 1327 1334 control control VBP 1335 1345 expression expression NN 1346 1348 of of IN 1349 1350 a a DT 1351 1355 gene gene NN 1356 1364 encoding encode VBG 1365 1366 a a DT 1367 1369 B7 b7 NN 1370 1383 costimulatory costimulatory JJ 1384 1392 molecule molecule NN 1392 1393 . . .