Fig. 6: TBL1X and TBL1XR1 requirement for β-cell function is conserved between rodents and humans.

a IgG (negative control), H3K27ac (positive control), TBL1X, TBL1XR1, and PAX6 ChIP-qPCR in EndoC-βH1 cells for the human INS locus. The enrichment is calculated over the negative locus and the IgG control. n = 3 individual experiments. b Endogenous TBL1X, TBL1XR1, HDAC3, and SPT16 were immunoprecipitated in EndoC-βH1 lysates with rabbit IgG as negative control. Whole cell lysates (Input) and immunoprecipitated proteins were immunoblotted using the indicated antibodies. Representative blot is shown for 4 independent experiments. c Human INS (hINS) promoter activity in INS1E cells upon TBL/R1 knockdown. Luciferase activity normalized to renilla luciferase. n = 4 wells/condition. d Insulin secretion relative to insulin content in EndoC-βH1 cells upon TBL/R1 knockdown. After glucose starvation, insulin secretion was stimulated using 2.8 mM glucose (2.8 G) and 2.8 mM glucose supplemented with KCl (KCl). n = 4 wells/condition. e Scatter plot depicting the relationship between HbA1c [%] and relative TBL1X mRNA levels determined by qPCR, adjusted for age, body mass index (BMI), and disease state. Each dot represents an individual data point. n = 31. f, g Manhattan plot showing an association between elevated HbA1c levels and single nucleotide polymorphisms in the genetic region of TBL1X (f) and TBL1XR1 (g). Data are represented as mean ± SEM. The following statistical tests were applied: two-sided student’s t test (a, c, d), and linear regression (e). Source data are provided as a Source Data file.