From the foregoing findings, a coherent picture emerges, suggesting that the transcriptional control of the INS/IGF2 locus in insulinomas, may, at least in part, switch from local or proximal PDX1-based transactivation to a more distal transcriptional regulation, driven by looping of the hypomethylated purple region containing the CTCF binding site within the SYT8/TNNI2 locus and/or other loci to the INS promoter, as first reported by Xu et al.12. The gene discussed is INS; the disease is pancreatic insulinoma.