Mitoepigenetics: Methylation of mitochondrial DNA is strand‐biased in bovine oocytes and embryos

Lima, Camila Bruna de; Sirard, Marc‐André

doi:10.1111/rda.13786

Cited by 4 publications

(4 citation statements)

References 8 publications

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“…Besides, the profile of methylated residues was associated to the origins of the oocyte (high-quality OPU-derived oocytes versus abattoir-derived oocytes) and was inversely correlated with differences in the expression of specific mitochondrial genes [ 21 ]. Furthermore, as observed in other studies, methylation was strand-biased and not restricted to CG context [ 22 ].…”

Section: Introductionsupporting

confidence: 76%

Genome-wide methylation profile of mitochondrial DNA across bovine preimplantation development

de Lima,

Martin,

Pecora Milazzotto

et al. 2023

Epigenetics

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This study characterized variations in the methylation profile of mitochondrial DNA (mtDNA) during initial bovine embryo development and correlated the presence of methylation with mtDNA transcription. Bovine oocytes were obtained from abattoir ovaries and submitted to in vitro culture procedures. Oocytes and embryos were collected at various stages (immature oocyte, IM; mature oocyte, MII; zygote, ZY; 4-cells, 4C; 16-cells, 16C and blastocysts, BL). Total DNA (including mtDNA) was used for Whole Genome Enzymatic Methyl Sequencing and for quantification of mtDNA copy number. Extracted RNA was used for quantification of mitochondrial transcripts using Droplet Digital PCR. We selected ND6, CYTB, tRNA-Phe and tRNA-Gln based on their location in the mitochondrial genome, functionality and/or previous literature associating these regions with cytosine methylation. The number of mtDNA copies per oocyte/embryo was found to be similar, while methylation levels in mtDNA varied among stages. Higher total methylation levels were found mainly at 4C and 16C. In specific gene regions, higher methylation levels were also observed at 4C and 16C (ND6, CYTB and tRNA-Phe), as well as an inverse correlation with the quantity of transcripts for these regions. This is a first description of epigenetic changes occurring in mtDNA during early embryonic development. Our results indicate that methylation might regulate the mtDNA transcription at a local level, particularly around the time of embryonic genome activation.

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Section: Introductionsupporting

confidence: 76%

Genome-wide methylation profile of mitochondrial DNA across bovine preimplantation development

de Lima,

Martin,

Pecora Milazzotto

et al. 2023

Epigenetics

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“…However, some differences between mtDNA and nuclear DNA methylation exist. Indeed, contrarily to genomic DNA, mtDNA showed to possess high levels of non-CpG versus CpG methylation, which is not symmetrical on both strands, being biased toward the L-strand, and it seems that depending on the cell type and context of cytosine methylation, mtDNA methylation can play a role in the regulation of mtDNA gene expression or mtDNA replication [ 46 , 50 , 54 , 60 , 61 , 62 ]. Additionally, 5-hmC has been detected in mtDNA, and there is evidence that 5-hmC marks are dynamic in nature and are enriched in the upstream of gene start site regions and in the gene body, similarly to nuclear genes [ 63 ].…”

Section: Mitoepigeneticsmentioning

confidence: 99%

Mitochondrial DNA Methylation and Human Diseases

Stoccoro

Coppedè

2021

IJMS

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Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

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“…We suggested that mtDNA methylation could be inherited from oocytes to early embryos since mtDNA methylation patterns were more conserved between oocytes and blastocysts than granulosa cells. Another recently published article from our team also indicated that the 5mC frequency is biased and not symmetrically distributed on both strands of bovine mitochondrial DNA in oocytes and embryos ( de Lima & Sirard, 2020 ). Mitochondrial DNA methylation may also respond to different environmental stressors such as metals, smoking, food supplements, drugs, and pollutants ( Sharma et al, 2019 ).…”

Section: Introductionmentioning

confidence: 79%