0 1 A a DT 2 9 central central JJ 10 14 role role NN 15 18 for for IN 19 20 a a DT 21 27 single single JJ 28 33 c-Myb c-myb NN 34 41 binding binding NN 42 46 site site NN 47 49 in in IN 50 51 a a DT 52 58 thymic thymic JJ 59 64 locus locus NN 65 72 control control NN 73 79 region region NN 79 80 . . . 82 87 Locus Locus NNP 88 95 control control NN 96 103 regions region NNS 104 105 ( ( ( 105 109 LCRs LCR NNPS 109 110 ) ) ) 111 114 are be VBP 115 123 powerful powerful JJ 124 134 assemblies assembly NNS 135 137 of of IN 138 141 cis cis NN 142 150 elements element NNS 151 155 that that WDT 156 164 organize organize VBP 165 168 the the DT 169 176 actions action NNS 177 179 of of IN 180 198 cell-type-specific cell-type-specific JJ 199 211 trans-acting trans-acting JJ 212 219 factors factor NNS 219 220 . . . 221 222 A a DT 223 229 2.3-kb 2.3-kb JJ 230 233 LCR lcr NN 234 236 in in IN 237 240 the the DT 241 246 human human JJ 247 256 adenosine adenosine NN 257 266 deaminase deaminase NNP 267 268 ( ( ( 268 271 ADA ADA NNP 271 272 ) ) ) 273 277 gene gene NN 278 283 first first JJ 284 290 intron intron NN 290 291 , , , 292 297 which which WDT 298 306 controls control VBZ 307 317 expression expression NN 318 320 in in IN 321 331 thymocytes thymocyte NNS 331 332 , , , 333 335 is be VBZ 336 344 composed compose VBN 345 347 of of IN 348 349 a a DT 350 356 200-bp 200-bp JJ 357 365 enhancer enhancer NN 366 372 domain domain NN 373 376 and and CC 377 385 extended extend VBD 386 394 flanking flanking NN 395 404 sequences sequence NNS 405 409 that that WDT 410 420 facilitate facilitate VBP 421 431 activation activation NN 432 436 from from IN 437 443 within within IN 444 453 chromatin chromatin NN 453 454 . . . 455 460 Prior prior JJ 461 469 analyses analysis NNS 470 474 have have VBP 475 487 demonstrated demonstrate VBN 488 492 that that IN 493 496 the the DT 497 505 enhancer enhancer NN 506 514 contains contain VBZ 515 516 a a DT 517 522 28-bp 28-bp JJ 523 527 core core NN 528 534 region region NN 535 538 and and CC 539 544 local local JJ 545 553 adjacent adjacent JJ 554 566 augmentative augmentative JJ 567 570 cis cis NN 571 579 elements element NNS 579 580 . . . 581 583 We we PRP 584 587 now now RB 588 592 show show VBP 593 597 that that IN 598 601 the the DT 602 606 core core NN 607 615 contains contain VBZ 616 617 a a DT 618 624 single single JJ 625 633 critical critical JJ 634 639 c-Myb c-myb NN 640 647 binding binding NN 648 652 site site NN 652 653 . . . 654 656 In in IN 657 661 both both DT 662 673 transiently transiently RB 674 687 cotransfected cotransfecte VBN 688 693 human human JJ 694 699 cells cell NNS 700 703 and and CC 704 710 stable stable JJ 711 731 chromatin-integrated chromatin-integrated JJ 732 737 yeast yeast NN 738 743 cells cell NNS 743 744 , , , 745 750 c-Myb c-myb NN 751 759 strongly strongly RB 760 774 transactivated transactivate VBD 775 783 reporter reporter NN 784 794 constructs construct NNS 795 799 that that WDT 800 809 contained contain VBD 810 821 polymerized polymerized JJ 822 826 core core NN 827 837 sequences. sequences. NN 838 843 c-Myb c-myb NN 844 851 protein protein NN 852 855 was be VBD 856 864 strongly strongly RB 865 872 evident evident JJ 873 875 in in IN 876 877 T t NN 878 890 lymphoblasts lymphoblast NNS 891 893 in in IN 894 899 which which WDT 900 903 the the DT 904 912 enhancer enhancer NN 913 916 was be VBD 917 923 active active JJ 924 927 and and CC 928 931 was be VBD 932 941 localized localize VBN 942 948 within within IN 949 957 discrete discrete JJ 958 965 nuclear nuclear JJ 966 976 structures structure NNS 976 977 . . . 978 983 Fetal fetal JJ 984 990 murine murine JJ 991 997 thymus thymus NN 998 1007 exhibited exhibit VBD 1008 1009 a a DT 1010 1018 striking striking JJ 1019 1030 concordance concordance NN 1031 1033 of of IN 1034 1044 endogenous endogenous JJ 1045 1050 c-myb c-myb NN 1051 1061 expression expression NN 1062 1066 with with IN 1067 1071 that that DT 1072 1074 of of IN 1075 1080 mouse mouse NN 1081 1084 ADA ADA NNP 1085 1088 and and CC 1089 1094 human human JJ 1095 1098 ADA ADA NNP 1099 1111 LCR-directed lcr-directed JJ 1112 1121 transgene transgene NN 1122 1132 expression expression NN 1132 1133 . . . 1134 1139 Point Point NNP 1140 1148 mutation mutation NN 1149 1151 of of IN 1152 1155 the the DT 1156 1161 c-Myb c-myb NN 1162 1166 site site NN 1167 1173 within within IN 1174 1177 the the DT 1178 1184 intact intact JJ 1185 1191 2.3-kb 2.3-kb JJ 1192 1195 LCR lcr NN 1196 1204 severely severely RB 1205 1215 attenuated attenuate VBD 1216 1224 enhancer enhancer NN 1225 1233 activity activity NN 1234 1236 in in IN 1237 1250 transfections transfection NNS 1251 1254 and and CC 1255 1258 LCR lcr NN 1259 1267 activity activity NN 1268 1270 in in IN 1271 1281 transgenic transgenic JJ 1282 1292 thymocytes thymocyte NNS 1292 1293 . . . 1294 1300 Within within IN 1301 1304 the the DT 1305 1312 context context NN 1313 1315 of of IN 1316 1317 a a DT 1318 1325 complex complex JJ 1326 1334 enhancer enhancer NN 1335 1338 and and CC 1339 1342 LCR LCR NNP 1342 1343 , , , 1344 1349 c-Myb c-myb NN 1350 1353 can can MD 1354 1357 act act VB 1358 1360 as as IN 1361 1363 an an DT 1364 1373 organizer organizer NN 1374 1376 of of IN 1377 1395 thymocyte-specific thymocyte-specific JJ 1396 1400 gene gene NN 1401 1411 expression expression NN 1412 1415 via via IN 1416 1417 a a DT 1418 1424 single single JJ 1425 1432 binding bind VBG 1433 1437 site site NN 1437 1438 . . .