This project will apply a comprehensive strategy to characterise and curate genome wide methylomes in liver tissues from rats and mouse. This will involve correlation of the profiles generated with public data sets for RNA expression (transcriptomics) and histone modification profiles with an emphasis on histone H3K4me1 (self-generated for rat), H3K4me3, H3K27me3 and Histone H3K36me3, which we believe will be informative with respect to genome organisation and activity i.e. promoters (active and inactive), gene bodies, enhancers, non-coding RNAs, repeats, endogenous retro-viruses (ERVs) and intra-genomic regions such as partially methylated domains (PMDs) (5,12,13). This data will be subsequently used for interrogation of the drug-metabolism gene repertoire including cytochrome p-450’s, GST’s, receptors (ER, AR, PR, Ah, PPRalpha and gamma, CAR etc) and UDP-glucuronosyltransferases (UGTs) (20,21). The results will be utilized for the main objective, namely to provide a comprehensive benchmark of the methylome of rodent strains in relation to normal liver function. This will provide the basis for understanding liver development, improved drug safety, investigating the underlying mechanisms of toxiciological response, increase the efficiency of drug development, and lead to progress with 3R issues (22).
Epigenomic profiling of liver tissue from Rat and Mice strains with toxicological relevance, presented at the 16th Cefic-LRI Annual Workshop 2014