Genome-wide analysis of transcriptional regulation in the murine liver.

摘要

The liver is a primary organ for toxicant metabolism in the body. This metabolism in influenced by genetic polymorphisms that can alter protein structure and influence gene expression levels in an allele specific manner. These polymorphisms produce significant differences in toxicant metabolism across human populations and an understanding of their influence on gene expression will improve our ability to predict toxic outcomes from chemical exposures. In order to understand the influence of polymorphisms on gene expression across populations, we studied liver gene expression in a model system consisting of two panels of laboratory inbred mice. We performed gene expression quantitative trait locus mapping in both panels of mice to discover polymorphisms that influence gene expression through both local and distant mechanisms and found several regions of the genome that regulate large numbers of genes in the liver. We examined the effect of sex of liver gene expression in one of the mouse panels and found significant differences between the sexes in many genes involved in xenobiotic metabolism. We also found that while gene expression level differences between sexes are important, there are also important differences in correlation between sets of genes in each sex. Finally, we studied the effect miRNAs on gene expression levels in the mouse liver and found, surprisingly, that their effect is mild. This report adds several new discoveries to the literature on transcriptional regulation in the liver and improves our understanding of the complex factors that control constitutive gene expression.