Construction and Application of an Epigenetic Atlas of the Human Heart
Date
2019-12-19
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Abstract
Epigenetic modifications, including DNA methylation, regulate gene expression and contribute to the specialization of cells. Currently, there is limited knowledge of the epigenetic patterns of the human heart. To address this gap, we generated methylation profiles for all distinct regions of the human heart. We hypothesized that unique differentially methylated regions (DMRs) of DNA exist for each cardiac region and that changes in DNA methylation occur in diverse cardiac diseases such as heart failure (HF) and congenital heart disease (CHD). Using healthy cardiac tissues and reduced representation bisulfite sequencing on the Illumina platform, we generated genome-wide methylomes in triplicate for the human right atrium, left atrium, right ventricle, left ventricle, aorta, pulmonary artery, mitral valve, tricuspid valve, aortic valve and pulmonary valve. We also generated methylomes (in triplicate) from the left ventricle of adult patients with HF and children with CHD. DMRs, defined as regions with significantly different mean methylation differences, were identified using the software package Metilene. For each tissue we generated 10-20 million reads covering 8-10 million CpG methylation sites across the genome and identified 5-57 tissue-specific DMRs. We identified 290 unique DMRs in the HF group and 317 in the CHD group. Potential disease-associated genes identified from this analysis included FGFR2, TOM22, HEX3 for HF and ROCK1 and MSX1 for CHD. In conclusion, we have created a DNA methylation atlas of the human heart. This data provides a resource for future studies and may help to identify new disease biomarkers and increase our understanding of cardiac development.
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Keywords
DNA methylation, human heart, RRBS
Citation
Prasher, D. (2019). Construction and Application of an Epigenetic Atlas of the Human Heart (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.