(a) Schematic illustrating the five putative CRE sites in the IP3R2 promoter. (b) HepG2 cells transfected with 1.5 kb or 1.0 kb segments of the IP3R2 promoter showed >20-fold greater activity when co-transfected with CREB, relative to empty vector (*p<0.0001, n=4), while mutation of CRE4, CRE5, or both markedly reduced activation by CREB (#p<0.001, n=4). There was no effect when CRE sites 1, 2 or 3 were mutated (not shown). (c) Summary of qPCR ChIP assay experiments shows that there was no enrichment in the CREB binding to CRE’s 1 and 2–3 over IgG control, but CREB binding was higher to CRE4 and 5. The increase was significant for CRE5 (*p<0.01, n=3) and marginally significant for CRE4 (0.1>p>0.05, n=3) compared to IgG. (d) Representative ChIP assay.