Comparative Analysis of Insulin Gene Promoters: Implications for Diabetes Research

Colin W. Hay; Kevin Docherty


Diabetes. 2006;55(12):3201-3213. 

In This Article

Multiple-Species Comparison of Insulin Promoters

There is no general approach to interpreting and predicting transcriptional evolution; however, the insulin promoter is one of the most extensively studied, and knowledge of the signals that bear upon insulin transcriptional regulation facilitates our understanding of possible functional consequences of insulin promoter evolutionary differences. By classic convention, the sequences that regulate basal promoters were divided into two classes. These are upstream regulatory elements (UREs) that are often located within 100–200 bp upstream of the site of initiation and display directional qualities, and enhancers that can function over distances of many kilobase pairs, regardless of orientation or whether they lie upstream or downstream of the start site. However, as more promoters and enhancers have been identified and studied, it has become apparent that there is a continuum between these two classes of regulatory elements with promoter and enhancer motifs sharing many physical and functional traits. Therefore, in keeping with current opinion, we have reviewed the cis-regulatory elements within the compact insulin promoter without further categorization.

This review has drawn upon publicly available DNA sequences to compare the human insulin promoter sequence (–1,500 to +100) to the insulin promoters in an evolutionary and taxonomically divergent range of species. Definitive identification of insulin genes and their promoters lags well behind the isolation of the corresponding cDNA sequences; hence, care has been taken to ensure that only unambiguous insulin promoters have been included. These belong to human (Homo sapiens), great apes (chimpanzee [Pan troglodytes], orangutan [Pongo pygmaeus], and gorilla [Gorilla gorilla]), Old World monkeys (African green monkey [Cercopithecus aethiops] and rhesus macaque [Macaca mulatta]), New World monkey (owl monkey [Aotus trivirgatus]), rodents (rat [Rattus norvegicus] and mouse [Mus musculus]), mammals with diverse diets (carnivorous dog [Canis familiaris], herbivorous cow [Bos taurus], and omnivorous pig [Sus scrofa]), bird (chicken [Gallus gallus]), and fish (zebrafish [Danio rerio]). The promoter sequences of gorilla, orangutan, African green monkey, and owl monkey are currently incomplete extending upstream to positions –295, –290, –426, and –510, respectively. The phylogenic relationships based on molecular analyses[32,33] between these species are outlined in Fig. 2.

Figure 2.

Phylogenic relationship between studied species. Evolutionary lineages of the studied species based on molecular analyses with branch lengths corresponding to time since divergence.


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