ArticleNucleic acids research2012
Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 194 citations in OpenAlex.
- Elevated mtDNA copy number in older adults is linked to methylation of mitochondrial and nuclear regulatory regions.GeroScience · 2026Article
- Organ-Specific Mitochondrial DNA Copy Number Responses in Neonatal Mice Following in Utero Irradiation.International journal of molecular sciences · 2026Article
- Nuclear Transfer Perturbs Genomic Balance.Epigenomes · 2026Article
- Regulation of mitochondrial function during spermatogenesis and sperm maturation.Cellular & molecular biology letters · 2026Review
- Modulation of mitochondrial DNA copy number: therapeutic potential of phytochemicals and plant extracts-a comprehensive review.Archives of pharmacal research · 2026Review
- Accumulated mtDNA mutations are linked to specific impairments in NADH-linked respiration.iScience · 2026Article
- The need to understand the underlying mechanisms associated with mitochondrial therapies in assisted reproduction before further clinical trials are performed.Human reproduction (Oxford, England) · 2026Review
- Mitochondria and the epigenome: maternal co-inheritance and crosstalk from oocyte to embryo.Cell communication and signaling : CCS · 2026Review
- The nuclear and mitochondrial genomes need to tango. How is their dance synchronized during development?NAR molecular medicine · 2026Article
- Newborn mitochondrial DNA copy number is associated with changes to DNA methylation that persist into childhood and are associated with cognitive development.Clinical epigenetics · 2025Article
- DJ-1 deficiency and aging: dual drivers of retinal mitochondrial dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Disruption of mitochondrial DNA integrity in cardiomyocyte injury upon ischemia/reperfusion.Genes & diseases · 2025Review
- Associations of Prenatal Mercury Exposure and PUFA with Telomere Length and mtDNA Copy Number in 7-Year-Old Children in the Seychelles Child Development Nutrition Cohort 2.Environmental health perspectives · 2025Article
- A Review over Mitochondrial Diseases Due to mtDNA Mutations: Recent Advances and Remedial Aspects.Infectious disorders drug targets · 2025Review
- Inference of forensic body fluids/tissues based on mitochondrial DNA copy number: a preliminary study.International journal of legal medicine · 2024Article
- Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.Epigenomes · 2024Article
- Whole Mitochondrial DNA Sequencing Using Fecal Samples from Domestic Dogs.Animals : an open access journal from MDPI · 2024Article
- Mitochondrial genome copy number variation across tissues in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A PCR-independent approach for mtDNA enrichment and next-generation sequencing: comprehensive evaluation and clinical application.Journal of translational medicine · 2024Article
- Mitochondrial aminoacyl-tRNA synthetases trigger unique compensatory mechanisms in neurons.Human molecular genetics · 2024Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is an essential mechanism controlling gene expression during differentiation and development. We investigated the epigenetic regulation of the nuclear-encoded, mitochondrial DNA (mtDNA) polymerase γ catalytic subunit (PolgA) by examining the methylation status of a CpG island within exon 2 of PolgA. Bisulphite sequencing identified low methylation levels (<10%) within exon 2 of mouse oocytes, blastocysts and embryonic stem cells (ESCs), while somatic tissues contained significantly higher levels (>40%). In contrast, induced pluripotent stem (iPS) cells and somatic nuclear transfer ESCs were hypermethylated (>20%), indicating abnormal epigenetic reprogramming. Real time PCR analysis of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) immunoprecipitated DNA suggests active DNA methylation and demethylation within exon 2 of PolgA. Moreover, neural differentiation of ESCs promoted de novo methylation and demethylation at the exon 2 locus. Regression analysis demonstrates that cell-specific PolgA expression levels were negatively correlated with DNA methylation within exon 2 and mtDNA copy number. Finally, using chromatin immunoprecipitation (ChIP) against RNA polymerase II (RNApII) phosphorylated on serine 2, we show increased DNA methylation levels are associated with reduced RNApII transcriptional elongation. This is the first study linking nuclear DNA epigenetic regulation with mtDNA regulation during differentiation and cell specialization.
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