Figure 1

Combined ablation of SREBP1 and SREBP2 induces a transcriptional program indicative of endoplasmic reticulum-stress activation. RNA from cells after silencing of control (siCtr), SREBP1 (siBP1), SREBP2 (siBP2) or both (siBP1 + 2) treated with 100 nM 4-OHT or solvent (ethanol) for 24 hours in medium containing 1% lipoprotein deficient serum (LPDS) was used for microarray analysis. Genes regulated in response to combined silencing of SREBP1 and SREBP2 were identified using a false discovery rate (FDR) of 0.01. (A) Heat map showing a two-way cluster analysis of the 417 genes regulated in response to silencing of SREBP1 and SREBP2. (B) Transcription factors (TFs) associated with genes regulated in response to SREBP1 and SREBP2 silencing. r: number of targets in the dataset regulated by this TF; n: number of network objects in the dataset; R: number of targets in the database regulated by this TF; N: total number of gene-based objects in the database; mean: mean value for hypergeometric distribution (n*R/N); z-score: z-score ((r-mean)/sqrt(variance)); P-value: probability to have the given value of r or higher (or lower for negative z-scores). (C) Gene set enrichment analysis (GSEA) was used to study association with transcriptional response to endoplasmic reticulum (ER)-stress. Enrichment plot of gene sets of ATF4, XBP-1 and ATF6 target genes from the literature. (D) Enrichment scores for gene sets derived from the literature. LU_2004_ATF4_select: Table 1 from Lu et al. [24]. ADACHI_2008_ATF6: Table 1 from Adachi et al. [16]. LU_2004_ATF4_all: Additional file 2: Table S1 from Lu et al. [24]. ACOSTA_ALVEAR_2007_XBP1: Table S5 from Acosta-Alvear et al. [25]. SIZE = number of genes within set; NES = Normalized Enrichment Score; q-value = FDR-adjusted P-value.