0 12 Coactivation Coactivation NNP 13 15 by by IN 16 21 OCA-B OCA-B NNP 21 22 : : : 23 33 definition definition NN 34 36 of of IN 37 45 critical critical JJ 46 53 regions region NNS 54 57 and and CC 58 67 synergism synergism NN 68 72 with with IN 73 80 general general JJ 81 90 cofactors cofactor NNS 90 91 . . . 93 102 Molecular molecular JJ 103 113 dissection dissection NN 114 116 of of IN 117 120 the the DT 121 136 B-cell-specific b-cell-specific JJ 137 150 transcription transcription NN 151 162 coactivator coactivator NN 163 168 OCA-B oca-b NN 169 172 has have VBZ 173 181 revealed reveal VBN 182 190 distinct distinct JJ 191 198 regions region NNS 199 208 important important JJ 208 209 , , , 210 222 respectively respectively RB 222 223 , , , 224 227 for for IN 228 239 recruitment recruitment NN 240 242 to to TO 243 257 immunoglobulin immunoglobulin NN 258 267 promoters promoter NNS 268 275 through through IN 276 287 interaction interaction NN 288 292 with with IN 293 306 octamer-bound octamer-bound JJ 307 312 Oct-1 oct-1 NN 313 316 and and CC 317 320 for for IN 321 331 subsequent subsequent JJ 332 343 coactivator coactivator NN 344 352 function function NN 352 353 . . . 354 361 Further further JJ 362 370 analysis analysis NN 371 373 of of IN 374 381 general general JJ 382 393 coactivator coactivator NN 394 406 requirements requirement NNS 407 413 showed show VBD 414 418 that that IN 419 428 selective selective JJ 429 436 removal removal NN 437 439 of of IN 440 443 PC4 pc4 NN 444 448 from from IN 449 452 the the DT 453 462 essential essential JJ 463 466 USA USA NNP 467 475 fraction fraction NN 476 484 severely severely RB 485 492 impairs impair VBZ 493 498 Oct-1 oct-1 NN 499 502 and and CC 503 508 OCA-B oca-b NN 509 517 function function NN 518 520 in in IN 521 522 a a DT 523 532 cell-free cell-free JJ 533 539 system system NN 540 553 reconstituted reconstitute VBN 554 558 with with IN 559 568 partially partially RB 569 577 purified purify VBN 578 585 factors factor NNS 585 586 . . . 587 591 Full full JJ 592 600 activity activity NN 601 604 can can MD 605 607 be be VB 608 616 restored restore VBN 617 619 by by IN 620 623 the the DT 624 632 combined combined JJ 633 639 action action NN 640 642 of of IN 643 654 recombinant recombinant JJ 655 658 PC4 pc4 NN 659 662 and and CC 663 666 the the DT 667 679 PC4-depleted pc4-depleted JJ 680 683 USA USA NNP 684 692 fraction fraction NN 692 693 , , , 694 698 thus thus RB 699 709 suggesting suggest VBG 710 711 a a DT 712 717 joint joint JJ 718 729 requirement requirement NN 730 733 for for IN 734 737 PC4 pc4 NN 738 741 and and CC 742 749 another another DT 749 750 , , , 751 762 USA-derived usa-derived JJ 763 775 component(s) component(s) NN 776 779 for for IN 780 787 optimal optimal JJ 788 796 function function NN 797 799 of of IN 800 811 Oct-1/OCA-B oct-1/oca-b NN 812 814 in in IN 815 818 the the DT 819 832 reconstituted reconstitute VBN 833 839 system system NN 839 840 . . . 841 847 Indeed indeed RB 847 848 , , , 849 860 USA-derived usa-derived JJ 861 864 PC2 pc2 NN 865 868 was be VBD 869 874 found find VBN 875 877 to to TO 878 881 act act VB 882 897 synergistically synergistically RB 898 902 with with IN 903 906 PC4 pc4 NN 907 909 in in IN 910 921 reproducing reproduce VBG 922 925 the the DT 926 934 function function NN 935 937 of of IN 938 944 intact intact JJ 945 948 USA USA NNP 949 951 in in IN 952 955 the the DT 956 961 assay assay NN 962 968 system system NN 968 969 . . . 970 980 Consistent consistent JJ 981 985 with with IN 986 989 the the DT 990 1001 requirement requirement NN 1002 1005 for for IN 1006 1009 PC4 pc4 NN 1010 1012 in in IN 1013 1016 the the DT 1017 1030 reconstituted reconstitute VBN 1031 1037 system system NN 1037 1038 , , , 1039 1044 OCA-B OCA-B NNP 1045 1048 was be VBD 1049 1054 found find VBN 1055 1057 to to TO 1058 1066 interact interact VB 1067 1075 directly directly RB 1076 1080 with with IN 1081 1084 PC4 pc4 NN 1084 1085 . . . 1086 1098 Surprisingly surprisingly RB 1098 1099 , , , 1100 1107 however however RB 1107 1108 , , , 1109 1116 removal removal NN 1117 1119 of of IN 1120 1123 PC4 pc4 NN 1124 1128 from from IN 1129 1132 the the DT 1133 1147 unfractionated unfractionated JJ 1148 1155 nuclear nuclear JJ 1156 1163 extract extract NN 1164 1167 has have VBZ 1168 1170 no no DT 1171 1182 detrimental detrimental JJ 1183 1189 effect effect NN 1190 1192 on on IN 1193 1214 OCA-B/Oct-1-dependent oca-b/oct-1-dependent JJ 1215 1228 transcription transcription NN 1228 1229 . . . 1230 1235 These these DT 1236 1243 results result NNS 1244 1248 lead lead VBP 1249 1251 to to TO 1252 1253 a a DT 1254 1261 general general JJ 1262 1267 model model NN 1268 1271 for for IN 1272 1275 the the DT 1276 1287 synergistic synergistic JJ 1288 1296 function function NN 1297 1299 of of IN 1300 1310 activation activation NN 1311 1318 domains domain NNS 1319 1321 in in IN 1322 1327 Oct-1 Oct-1 NNP 1328 1331 and and CC 1332 1337 OCA-B OCA-B NNP 1338 1339 ( ( ( 1339 1347 mediated mediate VBN 1348 1350 by by IN 1351 1354 the the DT 1355 1363 combined combined JJ 1364 1370 action action NN 1371 1373 of of IN 1374 1377 the the DT 1378 1386 multiple multiple JJ 1387 1390 USA USA NNP 1391 1401 components component NNS 1401 1402 ) ) ) 1403 1406 and and CC 1406 1407 , , , 1408 1415 further further RB 1415 1416 , , , 1417 1424 suggest suggest VBP 1425 1426 a a DT 1427 1437 functional functional JJ 1438 1448 redundancy redundancy NN 1449 1451 in in IN 1452 1459 general general JJ 1460 1472 coactivators coactivator NNS 1472 1473 . . .