Figure 7.

A hypothetical model depicting the functional role of YY1 in regulating glucose metabolism in pancreatic β cells. Under homeostasis, YY1 can directly bind to the enhancer regions of Ins1 and Ins2 or to the superenhancer region of Ins2. YY1 can also directly bind to the RNA pol II, potentially stabilizing the enhancer–promoter interaction through the multiprotein-DNA complex formation during gene transcription in pancreatic β-cells after birth. On the other hand, β-cell loss of Yy1 leads to reduced transcription and production of INS. Therefore, cKO mice develop characteristics of type 1 diabetes manifested as hyperglycemia, hypoinsulinemia, and impaired glucose tolerance as a result of impaired INS production. Taken together, YY1 is a novel transcriptional activator of the INS genes in pancreatic β-cells.