Fig. 7: CREB cooperates with CRTC2 to facilitate the transcription of KMT5C.

a Kmt5c mRNA levels in the fasted mice livers. Eight-week-old mice were fasting for 6, 12, 18, and 24 h, followed by quantitative PCR analysis (n = 4 for each group, male mice). b Primary hepatocytes were infected with HA-Creb1 lentivirus for 48 h, followed by chromatin immunoprecipitation (ChIP) using an HA antibody. The enrichment of the Kmt5c promoter was quantified by quantitative PCR analysis (n = 3 per group). c–f Quantitative PCR analysis (c, d) (n = 5 per group, male mice) and representative western blot analysis (f) (n = 4 per group, male mice) in the livers of mice. Ten-week-old mice were infused with shRNA plasmids against Creb1, Crtc2 through tail vein injection. Then the mice were fasted for 16 h following the gene expression analysis. The quantification of (f) was shown in (e). g–i Quantitative PCR (g) (n = 6 per group, male mice) and western blot analysis (i) (n = 6 per group, male mice) in the livers of mice. Ten-week-old mice were infused with pCMV vector or pCMV-Creb1 plasmids via tail vein injection. The mice were euthanized 16 h after injection at a fed state. The quantification of (i) was shown in (h). j A model for KMT5C regulating gluconeogenesis. CRTC2 cooperates with CREB1 to activate Kmt5c transcription in response to glucagon. KMT5C retards RNF34-mediated PGC-1α ubiquitination and subsequent degradation to promote gluconeogenesis. a–e, g, h data present mean ± s.e.m. a, c–i n represent biologically independent animal; (b) n represents biologically independent cell samples. a one-way ANOVA; (b–e, g, h) two-tailed unpaired Student’s t test. All experiments were repeated independently three times with similar results. Source data are provided as a Source Data file.