Methylation profiling by bisulfite sequencing analysis of the mtDNA Non-Coding Region in replicative and senescent Endothelial Cells

Bianchessi, Valentina; Vinci, Maria; Nigro, Patrizia; Rizzi, Valeria; Farina, Floriana Maria; Capogrossi, Maurizio C.; Pompilio, Giulio; Gualdi, V.; Lauri, Antonella

doi:10.1016/j.mito.2016.02.004

Cited by 55 publications

(63 citation statements)

References 55 publications

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“…2b). Since several studies show the presence of CpH methylation in the mtDNA 13–15 , also the level of CpH methylation was analysed for our cell lines in both regions. This analysis revealed an average level of CpH methylation below 1% (Suppl.…”

Section: Resultsmentioning

confidence: 99%

“…MtDNA methylation has been suggested to play a role in D-loop formation and mtDNA replication 13, 15 , possibly via the regulation of 7S DNA primer formation 15 . To address this, we studied the effect of CpG (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Intriguingly, at the same time, emerging evidence based on a wide variety of techniques 10 , convincingly supports the existence of mtDNA methylation. Such supporting evidence, as reviewed by us elsewhere 11 , includes the discovery of a) a mitochondria-targeted human DNA methyltransferase 1 transcript variant (mtDNMT1) 12 , b) the presence of both CpG and CpH (where H is A, T or C) methylation 8, 12–15 and, importantly, c) correlations with diseases such as cancer 16 , Down syndrome 17 and diabetes 18 . Although several of these papers hint toward an effect of mtDNA methylation on mitochondrial gene expression 12, 16, 18–20 , a direct causal link has yet to be demonstrated.…”

Section: Introductionmentioning

confidence: 93%

“…This event may initiate the transcription of small stretches of the complementary H-strand around the origin of H-strand replication (O H ) by the mitochondrial DNA polymerase (POLG), resulting in the formation of a short DNA fragment (7S DNA) that together with the mtDNA forms a stable D-loop structure 26, 27 . Interestingly, it is in this region of the D-loop that Bianchessi et al observed the highest methylation frequency and greatest asymmetry of CpG and CpH methylation between both strands 15 . These findings point to a possible functional effect of mtDNA methylation on 7S DNA and/or D-loop formation.…”

Section: Introductionmentioning

confidence: 93%

“…MtDNA methylation may directly regulate mtDNA gene expression (as described above), or alternatively, some suggested that it may do so indirectly 23, 24 via the modulation of mtDNA replication 13, 15 . MtDNA replication begins with the transcription of a small (~100 bp) RNA strand (7S RNA) from the LSP.…”

Section: Introductionmentioning

confidence: 99%

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Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

Wijst

Tilburg

Ruiters

et al. 2017

Sci Rep

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Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtDNA methylation has not been demonstrated. Therefore, we targeted DNA methylating enzymes (modifying cytosine in the CpG or GpC context) to the mtDNA. Unexpectedly, mtDNA gene expression remained unchanged upon induction of CpG mtDNA methylation, whereas induction of C-methylation in the GpC context decreased mtDNA gene expression. Intriguingly, in the latter case, the three mtDNA promoters were differentially affected in each cell line, while cellular function seemed undisturbed. In conclusion, this is the first study which directly addresses the potential functionality of mtDNA methylation. Giving the important role of mitochondria in health and disease, unravelling the impact of mtDNA methylation adds to our understanding of the role of mitochondria in physiological and pathophysiological processes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

Wijst

Tilburg

Ruiters

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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Epigenetics in Mollusks

Fallet

2023

Epigenetics in Aquaculture

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Mitochondrial DNA: Epigenetics and environment

Sharma

Pasala

Prakash

2019

Environ and Mol Mutagen

120

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Maintenance of the mitochondrial genome is essential for proper cellular function. For this purpose, mitochondrial DNA (mtDNA) needs to be faithfully replicated, transcribed, translated, and repaired in the face of constant onslaught from endogenous and environmental agents. Although only 13 polypeptides are encoded within mtDNA, the mitochondrial proteome comprises over 1500 proteins that are encoded by nuclear genes and translocated to the mitochondria for the purpose of maintaining mitochondrial function. Regulation of mtDNA and mitochondrial proteins by epigenetic changes and post‐translational modifications facilitate crosstalk between the nucleus and the mitochondria and ultimately lead to the maintenance of cellular health and homeostasis. DNA methyl transferases have been identified in the mitochondria implicating that methylation occurs within this organelle; however, the extent to which mtDNA is methylated has been debated for many years. Mechanisms of demethylation within this organelle have also been postulated, but the exact mechanisms and their outcomes is still an active area of research. Mitochondrial dysfunction in the form of altered gene expression and ATP production, resulting from epigenetic changes, can lead to various conditions including aging‐related neurodegenerative disorders, altered metabolism, changes in circadian rhythm, and cancer. Here, we provide an overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post‐translational modifications of nucleoid proteins (as mitochondria lack histones). We also highlight the influence of xenobiotics such as airborne environmental pollutants, contamination from heavy metals, and therapeutic drugs on mtDNA methylation. Environ. Mol. Mutagen., 60:668–682, 2019. © 2019 Wiley Periodicals, Inc.

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Methylation profiling by bisulfite sequencing analysis of the mtDNA Non-Coding Region in replicative and senescent Endothelial Cells

Cited by 55 publications

References 55 publications

Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

Epigenetics in Mollusks

Mitochondrial DNA: Epigenetics and environment

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