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Published in final edited form as: Biochim Biophys Acta. 2012 Feb 2;1819(7):644–651. doi: 10.1016/j.bbagrm.2012.01.016

Fig. 7 — Long range contacts and biological function in the human insulin locus. A) Map of the region around the human insulin gene. Abbreviations: Ins, insulin; TH, tyrosine hydroxylase; Igf2, insulin like growth factor 2 (sense/antisense); ICR, imprinted control region (with binding sites for CTCF). Dotted lines indicate possible interactions between the insulin promoter region and other more distant genes, which were searched for by 4C and 3C methods [39]. B) Summary of results obtained in these experiments with pancreatic islets from multiple human donors. showing the interaction between the human insulin and SYT8 loci, separated by about 300kb in the genome. In islets, addition of glucose results in increase in the contact between the loci, measured by 3C, and stimulation of SYT8 expression (top right). Targeting of the insulin promoter with siRNA results in a decrease in SYT8 expression (bottom left). Knockdown of CTCF results in loss of contact between the genes, downregulation of SYT8, but no change in insulin expression (bottom middle). To study the role of SYT8 in islet function we knocked down SYT8 and found that this resulted in a decrease in insulin secretion (bottom right, and see following figure) [39].

Fig. 7 — Long range contacts and biological function in the human insulin locus. A) Map of the region around the human insulin gene. Abbreviations: Ins, insulin; TH, tyrosine hydroxylase; Igf2, insulin like growth factor 2 (sense/antisense); ICR, imprinted control region (with binding sites for CTCF). Dotted lines indicate possible interactions between the insulin promoter region and other more distant genes, which were searched for by 4C and 3C methods [39]. B) Summary of results obtained in these experiments with pancreatic islets from multiple human donors. showing the interaction between the human insulin and SYT8 loci, separated by about 300kb in the genome. In islets, addition of glucose results in increase in the contact between the loci, measured by 3C, and stimulation of SYT8 expression (top right). Targeting of the insulin promoter with siRNA results in a decrease in SYT8 expression (bottom left). Knockdown of CTCF results in loss of contact between the genes, downregulation of SYT8, but no change in insulin expression (bottom middle). To study the role of SYT8 in islet function we knocked down SYT8 and found that this resulted in a decrease in insulin secretion (bottom right, and see following figure) [39].