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Defining baseline epigenetic landscapes in the rat liver.


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.

SUBMITTER: Thomson JP 

PROVIDER: S-EPMC5957268 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Defining baseline epigenetic landscapes in the rat liver.

Thomson John P JP   Ottaviano Raffaele R   Buesen Roland R   Moggs Jonathan G JG   Schwarz Michael M   Meehan Richard R RR  

Epigenomics 20171113 12


<h4>Aim</h4>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  ...[more]

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