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Open Access Highly Accessed Research article

DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions

Masaki Takasugi1, Shintaro Yagi1, Keiji Hirabayashi1 and Kunio Shiota12*

Author Affiliations

1 Laboratory of Cellular Biochemistry, Department of Animal Resource Science/Veterinary Medical Sciences, the University of Tolyo, Tokyo 113-8657, Japan

2 National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8561, Japan

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BMC Genomics 2010, 11:481  doi:10.1186/1471-2164-11-481

Published: 19 August 2010



Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA), and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes) has not been comprehensively analyzed.


We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs). These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain.


A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions.