GSE25862
Mapping of INS promoter interactions reveals its role in long-range  regulation of SYT8 transcription
Insulin (INS) synthesis and secretion from pancreatic ß cells are tightly regulated;  their deregulation causes diabetes. Here we map INS-associated loci in human  pancreatic islets by 4C and 3C techniques and show that the INS gene physically  interacts with the SYT8 gene, located over 300 kb away. This interaction is  elevated by glucose and accompanied by increases in SYT8 expression.  Inactivation of the INS promoter by promoter-targeting siRNA reduces SYT8  gene expression. SYT8-INS interaction and SYT8 transcription are attenuated by  CTCF depletion. Furthermore, SYT8 knockdown decreases insulin secretion in  islets. These results reveal a non-redundant role for SYT8 in insulin secretion  and indicate that the INS promoter acts from a distance to stimulate SYT8  transcription. This suggests a function for the INS promoter in coordinating  insulin transcription and secretion through long-range regulation of SYT8  expression in human islets. Overall design: Circular Chromosome Conformation Capture (4C)-Seq experiments to profile interactions of INS promoter in human pancreatic  islets isolated from two donors: donor 1 and donor 2.