Abstract
Many mammalian genes are clustered on the genomes, and hence the genes in the same cluster can be regulated through a common regulatory element. We indeed showed previously that the perilipin/PEX11α gene pair is transactivated tissue-selectively by PPARγ and PPARα, respectively, through a common binding site. In the present study, we identified a gene, named GSPA, neighboring a canonical PPAR target, acyl-CoA oxidase (AOX) gene. GSPA expression was induced by a peroxisome proliferator, Wy14,643, in the liver of wild-type mice, but not PPARα-null mice. GSPA and AOX share the promoter and two peroxisome proliferator-response elements. GSPA mRNA was also found in the heart and skeletal muscle, as well as 3T3-L1 cells. GSPA encodes a protein of 161 amino acids that is enriched in 3T3-L1 cells. Even other gene pairs might be regulated through common sequence elements, and conversely it would be interesting how each gene is aptly regulated in clusters.
Highlights
Recent analyses of human and other mammalian genomes have revealed that unexpectedly a large number of proteincoding genes are clustered [1], being arranged head-to-head, tail-to-head, or tail-to-tail
Identification in silico of a gene sharing the promoter with the acyl-CoA oxidase (AOX) gene We searched for a gene that is located near a known peroxisome proliferatoractivated receptor (PPAR) target gene in the NCBI mouse genome map
We named the gene corresponding to Riken 2310004N24, GSPA
Summary
Recent analyses of human and other mammalian genomes have revealed that unexpectedly a large number of proteincoding genes are clustered [1], being arranged head-to-head, tail-to-head, or tail-to-tail. Many of the RNA products do not seem to code for proteins [3], and most of such noncoding RNAs are yet uncharacterized Given such clustered arrangements of transcribed regions, it would be inferred that two or more clustered genes (or transcriptional units) are possibly regulated by common cis-elements in considerable number of instances. A common peroxisome proliferator-response element (PPRE), which serves as a binding site of PPAR/RXR heterodimer [7], is located within the spacer region, 8.4 kb downstream of the PEX11α promoter, whereas 1.9 kb upstream of the perilipin promoter. In the liver, this PPRE confers the action of PPARα, leading to the induction of PEX11α by the PPARα ligands, peroxisome proliferators. Differential interactions with other transcriptional factors seem important [8]
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