0 5 Every every DT 6 14 enhancer enhancer NN 15 20 works work VBZ 21 25 with with IN 26 31 every every DT 32 40 promoter promoter NN 41 44 for for IN 45 48 all all PDT 49 52 the the DT 53 65 combinations combination NNS 66 72 tested test VBN 72 73 : : : 74 79 could could MD 80 83 new new JJ 84 94 regulatory regulatory JJ 95 103 pathways pathway NNS 104 110 evolve evolve VBP 111 113 by by IN 114 122 enhancer enhancer NN 123 132 shuffling shuffling NN 132 133 ? ? . 135 138 The the DT 139 148 promoters promoter NNS 149 152 and and CC 153 162 enhancers enhancer NNS 163 165 of of IN 166 170 cell cell NN 171 184 type-specific type-specific JJ 185 190 genes gene NNS 191 194 are be VBP 195 200 often often RB 201 210 conserved conserve VBN 211 213 in in IN 214 223 evolution evolution NN 223 224 , , , 225 228 and and CC 229 234 hence hence RB 235 238 one one PRP 239 244 might might MD 245 251 expect expect VB 252 256 that that IN 257 258 a a DT 259 264 given give VBN 265 273 enhancer enhancer NN 274 277 has have VBZ 278 285 evolved evolve VBN 286 288 to to TO 289 293 work work VB 294 298 best best RB 299 303 with with IN 304 307 its its PRP$ 308 311 own own JJ 312 320 promoter promoter NN 320 321 . . . 322 327 While while IN 328 332 this this DT 333 344 expectation expectation NN 345 348 may may MD 349 351 be be VB 352 360 realized realize VBN 361 363 in in IN 364 368 some some DT 369 374 cases case NNS 374 375 , , , 376 378 we we PRP 379 383 have have VBP 384 387 not not RB 388 393 found find VBN 394 402 evidence evidence NN 403 406 for for IN 407 409 it it PRP 409 410 . . . 411 412 A a DT 413 418 total total NN 419 421 of of IN 422 424 27 27 CD 425 437 combinations combination NNS 438 440 of of IN 441 450 different different JJ 451 460 promoters promoter NNS 461 464 and and CC 465 474 enhancers enhancer NNS 475 479 were be VBD 480 486 tested test VBN 487 489 by by IN 490 502 transfection transfection NN 503 507 into into IN 508 516 cultured culture VBN 517 522 cells cell NNS 522 523 . . . 524 526 We we PRP 527 532 found find VBD 533 537 that that IN 538 541 the the DT 542 550 relative relative JJ 551 561 efficiency efficiency NN 562 564 of of IN 565 568 the the DT 569 578 enhancers enhancer NNS 579 581 is be VBZ 582 595 approximately approximately RB 596 599 the the DT 600 604 same same JJ 604 605 , , , 606 618 irrespective irrespective JJ 619 621 of of IN 622 625 the the DT 626 630 type type NN 631 633 of of IN 634 642 promoter promoter NN 643 647 used use VBN 647 648 , , , 649 653 i.e. i.e. FW 653 654 , , , 655 660 there there EX 661 664 was be VBD 665 667 no no DT 668 674 strong strong JJ 675 685 preference preference NN 686 689 for for IN 690 693 any any DT 694 699 given give VBN 700 717 enhancer/promoter enhancer/promoter NN 718 729 combination combination NN 729 730 . . . 731 738 Notably notably RB 738 739 , , , 740 742 we we PRP 743 745 do do VBP 746 749 not not RB 750 753 see see VB 754 766 particularly particularly RB 767 773 strong strong JJ 774 787 transcription transcription NN 788 792 when when WRB 793 796 the the DT 797 811 immunoglobulin immunoglobulin NN 812 817 kappa kappa NN 818 826 enhancer enhancer NN 827 828 ( ( ( 828 830 or or CC 831 834 the the DT 835 849 immunoglobulin immunoglobulin NN 850 855 heavy heavy JJ 856 861 chain chain NN 862 870 enhancer enhancer NN 870 871 ) ) ) 872 874 is be VBZ 875 879 used use VBN 880 882 to to TO 883 891 activate activate VB 892 893 a a DT 894 899 kappa kappa NN 900 904 gene gene NN 905 913 promoter promoter NN 913 914 . . . 915 917 We we PRP 918 925 propose propose VBP 926 930 that that IN 931 932 a a DT 933 942 generally generally RB 943 953 permissive permissive JJ 954 971 enhancer/promoter enhancer/promoter JJ 972 983 interaction interaction NN 984 986 is be VBZ 987 989 of of IN 990 1002 evolutionary evolutionary JJ 1003 1010 benefit benefit NN 1011 1014 for for IN 1015 1021 higher high JJR 1022 1032 eukaryotes eukaryote NNS 1032 1033 : : : 1034 1036 by by IN 1037 1045 enhancer enhancer NN 1046 1055 shuffling shuffling NN 1055 1056 , , , 1057 1062 genes gene NNS 1063 1068 could could MD 1069 1071 be be VB 1072 1078 easily easily RB 1079 1086 brought bring VBN 1087 1092 under under IN 1093 1094 a a DT 1095 1098 new new JJ 1099 1103 type type NN 1104 1106 of of IN 1107 1124 inducibility/cell inducibility/cell NN 1125 1129 type type NN 1130 1141 specificity specificity NN 1141 1142 . . .