TABLE 2

Major regulatory elements in insulin promoters

SpeciesDivergence (MYA)Regulatory elements
AGGCREEC1SP1G1G2
Human03242:41111
Chimpanzee53242:41111
Gorilla6.43*242:31SNA11
Orangutan11.33*242:31SNA11§
Rhesus macaque233232:31111§
African green monkey253241:21011§
Owl monkey353121:41111
Pig651111:31001
Rat 1752112:41010
Rat 2752011:31010
Mouse 1752012:51011
Mouse 2752011:41011
Dog922211:41001
Cow941111:21001
Chicken3102110:30000
Zebrafish4503010:20000
  • The numbers of the principal regulatory elements present in insulin promoters are listed. Given the complexity and uncertainty of predicting the transcriptional outcome of mutations within regulatory elements, certain assumptions have had to be made and are described below. Since CRE sites can display high variability and remain active, those containing single base pair differences from human have been included. The chicken and zebrafish insulin promoters share so little homology with mammals that the values for A boxes simply reflect the presence of TAAT motifs. Similarly, it is unclear whether any of their putative nonconsensus CRE sequences are functional. E box values are given as two numbers, with the first referring to the generally recognized E1 and E2 boxes and the second number representing all CANNTG sequences up to position −400 or the 5′ limit of available promoter sequence.

  • *

    * The genomic sequence for the A5 box is unavailable; however, it has been included in the table because the immediate downstream region shares 98% identity with the human and all other primates contain an A5 box;

  • lacks the consensus motif but contains the adjacent guanine-rich region (GAGA box), which is known to also function;

  • 1 bp substitution at position 2;

  • §

    § conservative transition at position 1 in the consensus motif;

  • the G2 site lies in a different location in comparison to human;

  • no certainty that the regulatory element functions. “Divergence” refers to time since divergence from human; MYA, millions of years ago; SNA, sequence not available.