0 4 ATF1 ATF1 NNP 5 8 and and CC 9 13 CREB CREB NNP 14 28 trans-activate trans-activate VBP 29 30 a a DT 31 35 cell cell NN 36 41 cycle cycle NN 42 51 regulated regulated JJ 52 59 histone histone NN 60 62 H4 h4 NN 63 67 gene gene NN 68 70 at at IN 71 72 a a DT 73 79 distal distal JJ 80 87 nuclear nuclear JJ 88 94 matrix matrix NN 95 105 associated associated JJ 106 114 promoter promoter NN 115 122 element element NN 122 123 . . . 125 133 Proteins Protein NNPS 134 136 of of IN 137 140 the the DT 141 149 ATF/CREB ATF/CREB NNP 150 155 class class NN 156 158 of of IN 159 172 transcription transcription NN 173 180 factors factor NNS 181 190 stimulate stimulate VBP 191 195 gene gene NN 196 206 expression expression NN 207 209 of of IN 210 217 several several JJ 218 222 cell cell NN 223 237 growth-related growth-related JJ 238 243 genes gene NNS 244 251 through through IN 252 259 protein protein NN 260 266 kinase kinase NNP 267 276 A-related a-related JJ 277 281 cAMP camp NN 282 290 response response NN 291 299 elements element NNS 299 300 . . . 301 304 The the DT 305 313 promoter promoter NN 314 322 activity activity NN 323 325 of of IN 326 330 cell cell NN 331 336 cycle cycle NN 337 346 regulated regulated JJ 347 354 histone histone NN 355 357 H4 h4 NN 358 363 genes gene NNS 364 366 is be VBZ 367 376 regulated regulate VBN 377 379 by by IN 380 382 at at IN 383 388 least least JJS 389 393 four four CD 394 403 principal principal JJ 404 414 cis-acting cis-acting JJ 415 423 elements element NNS 424 429 which which WDT 430 437 mediate mediate VBP 438 442 G1/S g1/s NN 443 448 phase phase NN 449 456 control control NN 457 463 and/or and/or CC 464 475 enhancement enhancement NN 476 478 of of IN 479 492 transcription transcription NN 493 499 during during IN 500 503 the the DT 504 508 cell cell NN 509 514 cycle cycle NN 514 515 . . . 516 521 Using use VBG 522 533 protein-DNA protein-dna JJ 534 545 interaction interaction NN 546 552 assays assay NNS 553 555 we we PRP 556 560 show show VBP 561 565 that that IN 566 569 the the DT 570 572 H4 h4 NN 573 581 promoter promoter NN 582 590 contains contain VBZ 591 594 two two CD 595 603 ATF/CREB ATF/CREB NNP 604 615 recognition recognition NN 616 622 motifs motif NNS 623 628 which which WDT 629 637 interact interact VBP 638 642 with with IN 643 647 CREB CREB NNP 647 648 , , , 649 653 ATF1 ATF1 NNP 653 654 , , , 655 658 and and CC 659 663 ATF2 atf2 NN 664 667 but but CC 668 671 not not RB 672 676 with with IN 677 687 ATF4/CREB2 atf4/creb2 NN 687 688 . . . 689 692 One one CD 693 700 ATF/CRE ATF/CRE NNP 701 706 motif motif NN 707 709 is be VBZ 710 717 located locate VBN 718 720 in in IN 721 724 the the DT 725 731 distal distal JJ 732 740 promoter promoter NN 741 743 at at IN 744 747 the the DT 748 755 nuclear nuclear JJ 756 773 matrix-associated matrix-associated JJ 774 778 Site Site NNP 779 781 IV iv CD 781 782 , , , 783 786 and and CC 787 790 the the DT 791 797 second second JJ 798 803 motif motif NN 804 806 is be VBZ 807 814 present present JJ 815 817 in in IN 818 821 the the DT 822 830 proximal proximal JJ 831 839 promoter promoter NN 840 842 at at IN 843 847 Site Site NNP 848 850 I. I. NNP 851 855 Both Both NNP 856 863 ATF/CRE ATF/CRE NNP 864 870 motifs motif NNS 871 878 overlap overlap VBP 879 886 binding binding NN 887 896 sequences sequence NNS 897 900 for for IN 901 904 the the DT 905 920 multifunctional multifunctional JJ 921 924 YY1 yy1 NN 925 938 transcription transcription NN 939 945 factor factor NN 945 946 , , , 947 952 which which WDT 953 956 has have VBZ 957 967 previously previously RB 968 972 been be VBN 973 978 shown show VBN 979 981 to to TO 982 984 be be VB 985 992 nuclear nuclear JJ 993 999 matrix matrix NN 1000 1010 associated associate VBN 1010 1011 . . . 1012 1022 Subnuclear subnuclear JJ 1023 1036 fractionation fractionation NN 1037 1044 reveals reveal VBZ 1045 1049 that that IN 1050 1055 there there EX 1056 1059 are be VBP 1060 1063 two two CD 1064 1068 ATF1 atf1 NN 1069 1077 isoforms isoform NNS 1078 1083 which which WDT 1084 1090 appear appear VBP 1091 1093 to to TO 1094 1100 differ differ VB 1101 1105 with with IN 1106 1113 respect respect NN 1114 1116 to to TO 1117 1120 DNA DNA NNP 1121 1128 binding binding NN 1129 1137 activity activity NN 1138 1141 and and CC 1142 1151 partition partition NN 1152 1163 selectively selectively RB 1164 1171 between between IN 1172 1179 nuclear nuclear JJ 1180 1186 matrix matrix NN 1187 1190 and and CC 1191 1200 nonmatrix nonmatrix JJ 1201 1213 compartments compartment NNS 1213 1214 , , , 1215 1225 consistent consistent JJ 1226 1230 with with IN 1231 1234 the the DT 1235 1239 role role NN 1240 1242 of of IN 1243 1246 the the DT 1247 1254 nuclear nuclear JJ 1255 1261 matrix matrix NN 1262 1264 in in IN 1265 1275 regulating regulate VBG 1276 1280 gene gene NN 1281 1291 expression expression NN 1291 1292 . . . 1293 1306 Site-directed site-directed JJ 1307 1317 mutational mutational JJ 1318 1325 studies study NNS 1326 1337 demonstrate demonstrate VBP 1338 1342 that that IN 1343 1347 Site Site NNP 1348 1349 I i CD 1350 1353 and and CC 1354 1358 Site Site NNP 1359 1361 IV iv CD 1362 1370 together together RB 1371 1378 support support VBP 1379 1384 ATF1- atf1- NN 1385 1388 and and CC 1389 1401 CREB-induced creb-induced JJ 1402 1418 trans-activation trans-activation NN 1419 1421 of of IN 1422 1425 the the DT 1426 1428 H4 h4 NN 1429 1437 promoter promoter NN 1437 1438 . . . 1439 1443 Thus thus RB 1443 1444 , , , 1445 1448 our our PRP$ 1449 1453 data datum NNS 1454 1463 establish establish VBP 1464 1468 that that IN 1469 1477 ATF/CREB ATF/CREB NNP 1478 1485 factors factor NNS 1486 1498 functionally functionally RB 1499 1507 modulate modulate VBP 1508 1515 histone histone NN 1516 1518 H4 h4 NN 1519 1523 gene gene NN 1524 1537 transcription transcription NN 1538 1540 at at IN 1541 1547 distal distal JJ 1548 1551 and and CC 1552 1560 proximal proximal JJ 1561 1569 promoter promoter NN 1570 1578 elements element NNS 1578 1579 . . .