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. 2022 Sep 30;298(11):102559. doi: 10.1016/j.jbc.2022.102559

Figure 5.

Figure 5

SIK inhibitors YKL-05-099 and SK-124 have PTH-like actions on the genome near Cyp27b1 and Cyp24a1.A, gene expression in the kidney for Cyp27b1 after WT mouse treatment with 30 mg/kg bw YKL-05-099 or 40 mg/kg bw SK-124 for 0, 0.5, 1, 3, 6, 12, 24 h (left) or 3 h YKL-05-099 at 7.5, 15, and 30 mg/kg bw and SK-124 at 40, 80, and 120 mg/kg bw (right). Data are displayed as relative quantitation (RQ, mean ± SEM) compared with Gapdh. n = 6 for time point. One-way ANOVA with multiple comparison Tukey post-test: ∗p < 0.05 time point or treatment versus 0 h. ChIP-Seq analysis near Cyp27b1 for (B) pCREB, (C) CBP, and (D) CRTC2 from WT mice injected with 230 mg/kg bw PTH for 30 min (PTH30), 30 mg/kg bw YKL-05-099 for 1 h, or 40 mg/kg bw SK-124. PTH30 data tracks are same as for Figure 2. Additional details as for Figure 2. Genomic region displayed is chr10: 126,469,260 to 126,490,800. E, Cyp24a1 expression in the mouse kidney after treatments described in A. ChIP-Seq analysis near Cyp24a1 for (F) pCREB, (G) CBP, and (H) CRTC2 as described above in B–D. PTH30 data tracks same as for Figure 3. Additional details as for Figure 2. Genomic region displayed is chr2: 170,278,379 to 170,324,235. bw, body weight; CBP, CREB-binding protein; ChIP-Seq, chromatin immunoprecipitation sequencing; CRTC, CREB-regulated transcription coactivator; pCREB, phosphorylated (p-133) CREB; PTH, parathyroid hormone; SIK, salt-inducible kinase.