FIG 3.

Loss of PTF1A disrupts the expression of genes for protein processing, packaging, and secretion, and it induces ER stress. (A and B) Changes in the expression of genes for the import of secretory protein into the RER, folding with disulfide bond formation, monitoring folding and ER stress control, ERAD, and apoptosis. (C) Quantification of the ratio of spliced to unspliced Xbp1 mRNA (n = 3 or 4 for each condition; *, P < 0.05). (D) Induction of the mRNAs of pancreatic stress proteins at 14 days; all FDR cutoffs were <10⁻⁸. (E) Decreased expression of newly identified or understudied genes highly expressed and largely restricted to the pancreas; all FDR cutoffs were <10⁻⁶, except for Rph3al (0.004). (F to H) Induction of clusterin (CLU) in acinar cells that lost PTF1A (arrowheads, examples of CLU⁺ cells; dashed lines, cells with PTF1A that do not stain for CLU; bar, 20 μm). (I to K) Increase of apoptotic cells (arrowheads) with activated caspase 3. Bar, 40 μm. (L) Relative number of apoptotic cells per field, corrected for cell density (n = 3 for each genotype/treatment; *, P < 0.05). (M to O) PTF1A binding in association with H3K4me2, RNAPII, and RBPJL at Cabp2, Sel1l, and Atf6.