Evidence map›Paper›PMID 37542258›Full record

ArticleBMC genomics2023

Optimized bisulfite sequencing analysis reveals the lack of 5-methylcytosine in mammalian mitochondrial DNA.

Zhenyu Shao, Yang Han, Dan Zhou

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Zhenyu ShaoState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. shaozhenyu2017@sibcb.ac.cn.
Yang HanShanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University & Chinese Academy of Medical Sciences (RU069), Shanghai, 200032, China.
Dan ZhouCenter for Medical Research and Innovation, Shanghai Pudong Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University & Chinese Academy of Medical Sciences (RU069), Shanghai, 201399, China. danzhou@fudan.edu.cn.
Shanghai Medical College of Fudan University · CNCenter for Excellence in Molecular Cell Science · CN

Funding

National Natural Science Foundation of China 32000420Natural Science Foundation of Shanghai 20ZR1408000
6 · The paper itself

Abstract

backgroundDNA methylation is one of the best characterized epigenetic modifications in the mammalian nuclear genome and is known to play a significant role in various biological processes. Nonetheless, the presence of 5-methylcytosine (5mC) in mitochondrial DNA remains controversial, as data ranging from the lack of 5mC to very extensive 5mC have been reported.

resultsBy conducting comprehensive bioinformatic analyses of both published and our own data, we reveal that previous observations of extensive and strand-biased mtDNA-5mC are likely artifacts due to a combination of factors including inefficient bisulfite conversion, extremely low sequencing reads in the L strand, and interference from nuclear mitochondrial DNA sequences (NUMTs). To reduce false positive mtDNA-5mC signals, we establish an optimized procedure for library preparation and data analysis of bisulfite sequencing. Leveraging our modified workflow, we demonstrate an even distribution of 5mC signals across the mtDNA and an average methylation level ranging from 0.19% to 0.67% in both cell lines and primary cells, which is indistinguishable from the background noise.

conclusionsWe have developed a framework for analyzing mtDNA-5mC through bisulfite sequencing, which enables us to present multiple lines of evidence for the lack of extensive 5mC in mammalian mtDNA. We assert that the data available to date do not support the reported presence of mtDNA-5mC.

Indexed as

5-MethylcytosineDNA, MitochondrialAnimalsDNA MethylationMammalsMitochondriaSequence Analysis, DNASulfites5-MethylcytosineDNA, Mitochondrialhydrogen sulfiteSulfitesBisulfite sequencingDNA methylationMitochondriaNUMTs

Identifiers

PMID37542258
PMCPMC10403921
OpenAlexW4385575467

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.