Defining baseline epigenetic landscapes in the rat liver. (December 2017)

• Record Type: Journal Article
• Authors: Thomson, John P; Ottaviano, Raffaele; Buesen, Roland; Moggs, Jonathan G; Schwarz, Michael; Meehan, Richard R
• Is Part Of: Epigenomics. Volume 9:Number 12(2017)
• Page Start: 1503
• Page End: 1527
• Publication Date: 2017-12
• Subjects: 5hmC -- 5-hydroxymethylation -- 5mC -- CpG methylation -- epigenetics -- rat -- strain -- toxicology; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2017-0029
• Languages: English
• ISSNs: 1750-1911

Abstract

Aim: Characterization of the hepatic epigenome following exposure to chemicals and therapeutic drugs provides novel insights into toxicological and pharmacological mechanisms, however appreciation of genome-wide inter- and intra-strain baseline epigenetic variation, particularly in under-characterized species such as the rat is limited. Material & methods: To enhance the utility of epigenomic endpoints safety assessment, we map both DNA modifications (5-methyl-cytosine and 5-hydroxymethyl-cytosine) and enhancer related chromatin marks (H3K4me1 and H3K27ac) across multiple male and female rat livers for two important outbred laboratory rat strains (Sprague–Dawley and Wistar).Results & conclusion: Integration of DNA modification, enhancer chromatin marks and gene expression profiles reveals clear gender-specific chromatin states at genes which exhibit gender-specific transcription. Taken together this work provides a valuable baseline liver epigenome resource for rat strains that are commonly used in chemical and pharmaceutical safety assessment.