Olivia H Cox, Fayaz Seifuddin, Jeffrey Guo, Mehdi Pirooznia, Gretha J Boersma, Josh Wang, Kellie L K Tamashiro, Richard S Lee
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引用次数: 0
Abstract
Epigenomic annotations for the rat lag far behind those of human and mouse, despite the rat's immense utility in pharmacological and behavioral studies and the need to understand their epigenetic mechanisms. We have designed a targeted-enrichment method followed by next-generation sequencing (Methyl-Seq) to identify DNA methylation (DNAm) signatures across the rat genome. The design reflected an attempt to create a more comprehensive investigation of the rat epigenome, as it included promoters, CpG islands, and island shores of all RefSeq genes. In this study, we implemented the rat Methyl-Seq platform and tested its ability to distinguish differentially methylated regions (DMRs) among three different tissue types, three distinct brain regions, and, in the hippocampus, between males and females. These comparisons yielded DNAm differences of differing magnitudes, many of which were independently validated by bisulfite pyrosequencing, including autosomal regions that were predicted to show the least degree of difference in DNAm between males and females. Quantitative reverse transcription PCR revealed that most genes associated with the DMRs showed tissue-, brain region-, and sex-specific differences in expression. In particular, we found evidence for sex-specific DNAm and expression differences at Tubb6, Lrrn2, Tex26, and Sox5l1, all of which play important roles in neurodevelopment and have been implicated in studies examining sex differences. Our results demonstrate the utility of the rat Methyl-Seq platform and suggest the presence of DNAm differences between the male and female hippocampus. The rat Methyl-Seq has the potential to provide epigenomic insights into pharmacological and behavioral studies performed in the rat.
期刊介绍:
Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed.
Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to):
DNA methylation
Nucleosome positioning and modification
Gene silencing
Imprinting
Nuclear reprogramming
Chromatin remodeling
Non-coding RNA
Non-histone chromosomal elements
Dosage compensation
Nuclear organization
Epigenetic therapy and diagnostics
Nutrition and environmental epigenetics
Cancer epigenetics
Neuroepigenetics