0 15 Tissue-specific tissue-specific JJ 16 26 regulation regulation NN 27 29 of of IN 30 33 the the DT 34 54 ecto-5’-nucleotidase ecto-5'-nucleotidase NN 55 63 promoter promoter NN 63 64 . . . 65 69 Role role NN 70 72 of of IN 73 76 the the DT 77 81 camp camp NN 82 90 response response NN 91 98 element element NN 99 103 site site NN 104 106 in in IN 107 116 mediating mediate VBG 117 127 repression repression NN 128 130 by by IN 131 134 the the DT 135 143 upstream upstream JJ 144 154 regulatory regulatory JJ 155 161 region region NN 161 162 . . . 164 166 We we PRP 167 171 have have VBP 172 180 isolated isolate VBN 181 184 the the DT 185 186 5 5 CD 186 187 ’ ' SYM 188 194 region region NN 195 197 of of IN 198 201 the the DT 202 222 ecto-5’-nucleotidase ecto-5'-nucleotidase NN 223 224 ( ( ( 224 227 low low JJ 228 232 K(m) k(m) NN 233 238 5’-NT 5'-nt NN 238 239 ) ) ) 240 244 gene gene NN 245 248 and and CC 249 260 established establish VBD 261 265 that that IN 266 267 a a DT 268 276 969-base 969-base JJ 277 281 pair pair NN 282 283 ( ( ( 283 285 bp bp NN 285 286 ) ) ) 287 295 fragment fragment NN 296 303 confers confer VBZ 304 317 cell-specific cell-specific JJ 318 328 expression expression NN 329 331 of of IN 332 333 a a DT 334 337 CAT CAT NNP 338 346 reporter reporter NN 347 351 gene gene NN 352 356 that that WDT 357 367 correlates correlate VBZ 368 372 with with IN 373 376 the the DT 377 387 expression expression NN 388 390 of of IN 391 401 endogenous endogenous JJ 402 412 ecto-5’-NT ecto-5'-nt JJ|NN 413 417 mRNA mrna NN 418 421 and and CC 422 431 enzymatic enzymatic JJ 432 440 activity activity NN 440 441 . . . 442 443 A a DT 444 450 768-bp 768-bp JJ 451 459 upstream upstream JJ 460 468 negative negative JJ 469 479 regulatory regulatory JJ 480 486 region region NN 487 490 has have VBZ 491 495 been be VBN 496 506 identified identify VBN 507 511 that that WDT 512 521 conferred confer VBD 522 541 lymphocyte-specific lymphocyte-specific JJ 542 550 negative negative JJ 551 561 regulation regulation NN 562 564 in in IN 565 566 a a DT 567 579 heterologous heterologous JJ 580 586 system system NN 587 591 with with IN 592 593 a a DT 594 600 244-bp 244-bp JJ 601 614 deoxycytidine deoxycytidine NN 615 621 kinase kinase NNP 622 626 core core NN 627 635 promoter promoter NN 635 636 . . . 637 642 DNase DNase NNP 643 644 I i CD 645 657 footprinting footprinting NN 658 668 identified identify VBD 669 676 several several JJ 677 686 protected protected JJ 687 692 areas area NNS 693 702 including include VBG 703 706 Sp1 Sp1 NNP 706 707 , , , 708 716 Sp1/AP-2 sp1/ap-2 NN 716 717 , , , 718 721 and and CC 722 726 cAMP camp NN 727 735 response response NN 736 743 element element NN 744 745 ( ( ( 745 748 CRE CRE NNP 748 749 ) ) ) 750 757 binding binding NN 758 763 sites site NNS 764 770 within within IN 771 774 the the DT 775 781 201-bp 201-bp JJ 782 786 core core NN 787 795 promoter promoter NN 796 802 region region NN 803 806 and and CC 807 810 Sp1 Sp1 NNP 810 811 , , , 812 818 NRE-2a NRE-2a NNP 818 819 , , , 820 831 TCF-1/LEF-1 TCF-1/LEF-1 NNP 831 832 , , , 833 836 and and CC 837 846 Sp1/NF-AT Sp1/NF-AT NNP 847 854 binding binding NN 855 860 sites site NNS 861 863 in in IN 864 867 the the DT 868 876 upstream upstream JJ 877 887 regulatory regulatory JJ 888 894 region region NN 894 895 . . . 896 903 Whereas whereas IN 904 907 the the DT 908 911 CRE CRE NNP 912 916 site site NN 917 920 was be VBD 921 930 essential essential JJ 931 933 in in IN 934 943 mediating mediate VBG 944 947 the the DT 948 956 negative negative JJ 957 965 activity activity NN 966 968 of of IN 969 972 the the DT 973 981 upstream upstream JJ 982 992 regulatory regulatory JJ 993 999 region region NN 1000 1002 in in IN 1003 1009 Jurkat Jurkat NNP 1010 1013 but but CC 1014 1017 not not RB 1018 1020 in in IN 1021 1025 HeLa HeLa NNP 1026 1031 cells cell NNS 1031 1032 , , , 1033 1041 mutation mutation NN 1042 1044 of of IN 1045 1048 the the DT 1049 1057 Sp1/AP-2 sp1/ap-2 NN 1058 1062 site site NN 1063 1072 decreased decrease VBD 1073 1081 promoter promoter NN 1082 1090 activity activity NN 1091 1093 in in IN 1094 1098 both both DT 1099 1103 cell cell NN 1104 1109 lines line NNS 1109 1110 . . . 1111 1126 Electrophoretic electrophoretic JJ 1127 1135 mobility mobility NN 1136 1141 shift shift NN 1142 1147 assay assay NN 1148 1156 analysis analysis NN 1157 1159 of of IN 1160 1168 proteins protein NNS 1169 1176 binding bind VBG 1177 1179 to to TO 1180 1183 the the DT 1184 1187 CRE CRE NNP 1188 1192 site site NN 1193 1203 identified identify VBD 1204 1208 both both CC 1209 1214 ATF-1 atf-1 NN 1215 1218 and and CC 1219 1224 ATF-2 atf-2 NN 1225 1227 in in IN 1228 1234 Jurkat Jurkat NNP 1235 1240 cells cell NNS 1240 1241 . . . 1242 1249 Finally finally RB 1249 1250 , , , 1251 1258 phorbol phorbol NN 1259 1271 12-myristate 12-myristate NN 1272 1282 13-acetate 13-acetate NN 1283 1292 increased increase VBD 1293 1296 the the DT 1297 1305 activity activity NN 1306 1308 of of IN 1309 1313 both both CC 1314 1317 the the DT 1318 1322 core core NN 1323 1326 and and CC 1327 1330 the the DT 1331 1337 969-bp 969-bp JJ 1338 1346 promoter promoter NN 1347 1356 fragments fragment NNS 1356 1357 , , , 1358 1361 and and CC 1362 1366 this this DT 1367 1375 increase increase NN 1376 1379 was be VBD 1380 1389 abrogated abrogate VBN 1390 1392 by by IN 1393 1402 mutations mutation NNS 1403 1405 at at IN 1406 1409 the the DT 1410 1413 CRE CRE NNP 1414 1418 site site NN 1418 1419 . . . 1420 1422 In in IN 1423 1430 summary summary NN 1430 1431 , , , 1432 1434 we we PRP 1435 1439 have have VBP 1440 1450 identified identify VBN 1451 1452 a a DT 1453 1468 tissue-specific tissue-specific JJ 1469 1479 regulatory regulatory JJ 1480 1486 region region NN 1487 1488 5 5 CD 1488 1489 ’ ' SYM 1490 1492 of of IN 1493 1496 the the DT 1497 1507 ecto-5’-NT ecto-5'-nt JJ|NN 1508 1512 core core NN 1513 1521 promoter promoter NN 1522 1526 that that WDT 1527 1535 requires require VBZ 1536 1539 the the DT 1540 1548 presence presence NN 1549 1551 of of IN 1552 1553 a a DT 1554 1564 functional functional JJ 1565 1568 CRE cre NN 1569 1573 site site NN 1574 1580 within within IN 1581 1584 the the DT 1585 1590 basal basal JJ 1591 1599 promoter promoter NN 1600 1603 for for IN 1604 1607 its its PRP$ 1608 1619 suppressive suppressive JJ 1620 1628 activity activity NN 1628 1629 . . .