In silico searching of human and mouse genome data identifies known and unknown HNF1 binding sites upstream of (beta)-cell genes

HNF1-(alpha) is a transcription factor present in (beta)-cells. Mutations in the HNF1-(alpha) gene cause maturity-onset diabetes of the young (MODY), but the exact mechanism is not known. Several studies have highlighted genes down-regulated in (beta)cells lacking this gene, but it is not clear if these are directly regulated by HNF1-(alpha). To better understand this, we used human and mouse genome data to examine 29 genes expressed in the (beta)-cell. Using an in silico approach (with software available at www.BindGene.org) we examined 2 kb upstream of each gene for possible HNF1 binding sequences. In five genes we also examined 100 kb upstream of each gene, but only the portions strongly conserved between humans and mice. We identified nine putative HNF1 binding sites upstream of seven genes (p<0.1 and good alignment between species or p <0.05). Six of these nine sites had some experimental corroboratory evidence and included the recently identified sites 6 and 45 kb upstream of HNF4-(alpha). Three novel sites were identified. These were 92 bp upstream of SLC3A1, 52 bp upstream of PCBD (DCOH), and 42202 bp upstream of TCF2(HNF1-(beta)). In conclusion, our computer search identified some known HNF1 sites, and suggested three novel sites indicating these genes are very likely to be directly activated by HNF1. This should help in designing experiments to discover the mechanisms of (beta)-cell dysfunction due to HNF1 disruption.