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. Author manuscript; available in PMC: 2010 Aug 18.
Published in final edited form as: Dev Cell. 2008 Dec;15(6):829–840. doi: 10.1016/j.devcel.2008.10.015

Figure 2.

Figure 2

Persistent ER stress in vivo suppresses expression of a subset of metabolic genes. (A) Cluster analysis of gene expression and transcriptional profiling analysis of liver RNAs were performed as described in the Experimental Procedures. Graphic representation of the average expression levels of 4262 differentially-expressed genes is shown. Each vertical bar represents a single gene. Green coloration indicates lower expression, and red indicates higher expression. (B, C) The expression levels of two subsets of mRNAs from microarray analysis are shown, normalized against vehicle-injected wild-type samples. Note that the differences in expression levels of these genes in the absence of ER stress were generally not significant. Error bars represent means ±S.D.M. from three animals in each group. For (B), all genes shown were significantly (p<0.05) less-induced by TM in Atf6α-null animals than wild-type. For (C), all genes shown were significantly (p<0.05) downregulated by stress in both genotypes. The ATF4-dependent tryptophanyl tRNA synthetase (Wars) is here Atf6α-dependent likely because of the failure of Atf6α-null mice to stimulate eIF2α phosphorylation in response to TM challenge. (D) Real-time RT-PCR analysis was used to assess the expression of selected mRNAs in wild-type or Atf6α-null livers 8 or 48 hours after TM injection. Error bars are means ±S.D.M. from 2 (vehicle) or 3 (TM) animals. Expression values were normalized against β-actin levels and are shown relative to the expression level in wild-type unchallenged animals. (E) Protein lysates from livers of wild-type or Atf6α−/− mice injected with vehicle or TM (1 mg/kg) were probed by immunoblot for either C/EBPα (which exists in a 42kd long form and 30kd short form) or C-JUN. (F, G) The expression of metabolic genes subdivided into various categories was determined 48 hours after TM injection by real-time RT-PCR. For (D, F, G, and H). Red lettering indicates genes significantly (p<0.05) different in expression comparing TM-challenged Atf6α-null animals to unchallenged.