Fig. 5: Qki-5 cooperates with Srebp2 to regulate transcription of cholesterol biosynthesis genes.

a Venn diagram showing the number of overlapping promoters bound by Qki-5, Srebp2, and Pol II from ChIP-seq in NLPCs. Promoters defined by TSS ± 2 kb. b DNA-binding motif similar to the known SREBP2 motif was enriched in QKI-5 ChIP-seq peaks in NLPCs and HLE-B3 cells using HOMER motif analysis. p-value was derived by HOMER using cumulative binomial distributions. c IPA of the top 1,000 genes (ranked according to RPM within ±0.5 kb of TSS in Srebp2 ChIP-seq) in overlapping binding promoters shown in a (n = 9,032). Canonical cellular pathways are ranked according to significance (p-value) (p < 0.05; right-tailed Fischer’s exact t-test). The blue labels the canonical cellular pathways including cholesterol biosynthesis genes. d Cholesterol biosynthesis pathway and genes encoding the enzymes involved in the cholesterol biosynthesis. Blue-labeled genes are clustered in the cholesterol biosynthesis pathway in c. e UCSC Genome Browser snapshot of the promoter regions of cholesterol biosynthesis genes encoding the cholesterol biosynthesis enzymes labeled in blue in d, which are co-bound by Qki-5, Srebp2, and Pol II in NLPCs. Input and rabbit IgG are used as controls. f Venn diagram showing the overlapping genes between Qki-5–bound genes from Qki-5 ChIP-seq data in NLPCs and downregulated genes in both Qk^-/- NLPCs and QKI KO HLE-B3 cells relative to WT according to RNA-seq (p < 0.05; two-tailed Wald test). DE: differentially expressed. g IPA of the overlapping genes in f (n = 301) ranked according to significance (p-value) (p < 0.05; right-tailed Fischer’s exact t-test). Cellular pathways involved in cholesterol biosynthesis are labeled in orange. h Comparison of the average RPM values of the Qki-5⁺Srebp2⁻ (n = 1,583) and Qki-5⁺Srebp2⁺ (n = 9,047) ChIP-seq binding events within ±0.5 kb from the TSS shown in NLPCs.