Journal article
Adaptation of the targeted capture Methyl-Seq platform for the mouse genome identifies novel tissue-specific DNA methylation patterns of genes involved in neurodevelopment
Epigenetics, Vol.10(7), pp.581-596
07/03/2015
DOI: 10.1080/15592294.2015.1045179
PMCID: PMC4622595
PMID: 25985232
Abstract
Methyl-Seq was recently developed as a targeted approach to assess DNA methylation (DNAm) at a genome-wide level in human. We adapted it for mouse and sought to examine DNAm differences across liver and 2 brain regions: cortex and hippocampus. A custom hybridization array was designed to isolate 99 Mb of CpG islands, shores, shelves, and regulatory elements in the mouse genome. This was followed by bisulfite conversion and sequencing on the Illumina HiSeq2000. The majority of differentially methylated cytosines (DMCs) were present at greater than expected frequency in introns, intergenic regions, near CpG islands, and transcriptional enhancers. Liver-specific enhancers were observed to be methylated in cortex, while cortex specific enhancers were methylated in the liver. Interestingly, commonly shared enhancers were differentially methylated between the liver and cortex. Gene ontology and pathway analysis showed that genes that were hypomethylated in the cortex and hippocampus were enriched for neuronal components and neuronal function. In contrast, genes that were hypomethylated in the liver were enriched for cellular components important for liver function. Bisulfite-pyrosequencing validation of 75 DMCs from 19 different loci showed a correlation of r = 0.87 with Methyl-Seq data. We also identified genes involved in neurodevelopment that were not previously reported to be differentially methylated across brain regions. This platform constitutes a valuable tool for future genome-wide studies involving mouse models of disease.
Details
- Title: Subtitle
- Adaptation of the targeted capture Methyl-Seq platform for the mouse genome identifies novel tissue-specific DNA methylation patterns of genes involved in neurodevelopment
- Creators
- Benjamin Hing - Department of Psychiatry; University of Iowa Carver College of MedicineEnrique Ramos - Department of Pediatrics and Center for Genome Sciences and Systems Biology; Washington University School of MedicinePatricia Braun - Department of Psychiatry; University of Iowa Carver College of MedicineMelissa McKane - Department of Psychiatry; University of Iowa Carver College of MedicineDubravka Jancic - Department of Psychiatry; University of Iowa Carver College of MedicineKellie L K Tamashiro - Department of Psychiatry and Behavioral Sciences; Johns Hopkins University School of MedicineRichard S Lee - Department of Psychiatry and Behavioral Sciences; Johns Hopkins University School of MedicineJacob J Michaelson - Department of Psychiatry; University of Iowa Carver College of MedicineTodd E Druley - Department of Pediatrics and Center for Genome Sciences and Systems Biology; Washington University School of MedicineJames B Potash - Department of Psychiatry; University of Iowa Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Epigenetics, Vol.10(7), pp.581-596
- Publisher
- Taylor & Francis
- DOI
- 10.1080/15592294.2015.1045179
- PMID
- 25985232
- PMCID
- PMC4622595
- ISSN
- 1559-2294
- eISSN
- 1559-2308
- Language
- English
- Date published
- 07/03/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070288802771
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