We have used expression microarrays to examine on a genome-wide scale the range of targets regulated by SBP-1, the C. elegans homolog of SREBP1 and SREBP2 (the Sterol Response Element Binding Proteins). In mammals, SREBP1 and SREBP2 have been well established as central to the regulation of cholesterol and fatty acid homeostasis. Lipid analysis of
sbp-1(RNAi) and
sbp-1 mutants has revealed low levels of triacylglycerides, and a range of fatty acid composition defects. In order to find the genes that act downstream of
sbp-1, we used the Affymetrix genomic microarray to perform comparisons between gene expression levels of the following strains: wild-type;
sbp-1(
ep79), a strong loss-of-function allele; and epEx307, a strain carrying a stable extrachromosomal array of SBP-1:GFP. As expected, the most significant differences were found between
sbp-1(
ep79) and epEx307: 530 genes were downregulated in
sbp-1(
ep79), while 342 were upregulated. Among the downregulated targets are a number of genes involved in fatty acid synthesis, desaturation, elongation and beta oxidation, indicating that the C. elegans SBP-1 acts at least partially on targets similar to those of its mammalian homologs. We further analyzed a subset of 40 of the downregulated genes using RNAi, followed by a number of phenotypic assays, and chose to concentrate on F22E10.5, a choline/ethanolamine phosphatidyltransferase (CEPT) and C31E10.7, a cytochrome
b5. Depletion of C31E10.7(cytochrome
b5) by RNAi causes very high levels of stearic acid, and low levels of polyunsaturated fatty acids, a phenotype similar to that of the
fat-6;
fat-7 double mutant, which is deficient in stearoyl-CoA desaturase (SCD) activity. Because cytochrome-
b5 mediated electron transfer is necessary for the desaturation reaction mediated by
fat-6 and
fat-7, we propose that C31E10.7 encodes the cytochrome
b5 that acts in concert with one or both of these genes. Inhibition of F22E10.5 (CEPT) by RNAi leads to low levels of phosphatidylcholine (PC), and marginally lower levels of phosphatidylethanolamine (PE). The fatty acid profile is similar to that of the three other genes predicted to be involved in the PC synthesis pathway: F08C6.2 (CTP-phosphocholine cytidylyltransferase),
cka-1, and
cka-2 (choline kinases). Interestingly, RNA inhibition of F08C6.2 leads to very strong nuclear localization of SBP-1:GFP, a step required for activation. Taken together, these results identify a novel role for SBP-1 in PC biosynthesis.