Abstract
Epigenetic modifications viz. DNA methylation, histone modifications, and RNA-based alterations play a crucial role in the development of cardiovascular diseases. In this study, we investigated DNA methylation with an aim to reveal the epigenetic etiology of heart failure. Sprague–Dawley rats surviving myocardial infarction developed acute heart failure in 1 week. Genomic DNA methylation changes were profiled by bisulfite sequencing, and gene expression levels were analyzed by RNA-seq in failing and sham-operation hearts. A total of 3480 differentially methylated genes in the promoter regions including transcriptional start site and 1934 transcriptome-altered genes were identified in the defected hearts. Common differential genes were enriched by the gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein–protein interaction for HF phenotypes. Among these, Mettl11b, HDAC3, HDAC11, ubiquitination-related genes, and snoRNAs are new epigenetic classifiers that had not been reported yet, which may be important regulators in HF.
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Acknowledgements
Thanks to “Beijing Biomarker Technology” and “Shanghai Bohao Biotechnology” for providing data analysis support.
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This work was supported by the National Natural Science Foundation of China (grants 81330007, U1601227, No. 81973320), the Science and Technology Programs of Guangdong Province (2015B020225006), and the Bureau of Education of Guangzhou Municipality Foundation (No. 201831836).
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ZXL, YZZ, and XYY designed the research. ZXL and JSC performed the research. ZXL analyzed the data and wrote the manuscript. XZL, JL W, XD W, XYL help to revise the manuscript.
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Lin, Z., Chang, J., Li, X. et al. Association of DNA methylation and transcriptome reveals epigenetic etiology of heart failure. Funct Integr Genomics 22, 89–112 (2022). https://doi.org/10.1007/s10142-021-00813-9
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DOI: https://doi.org/10.1007/s10142-021-00813-9