Eukaryotic DNA Methylation

DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such as regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine (5mC) but recently adenine methylation was also found to be present in eukaryotes. In mouse embryonic stem cells, 6-methyladenine (6mA) was associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and fetal development. In somatic cells there are clear tissue specificity in 6mA levels, with the highest 6mA levels being observed in the brain. In zebrafish, during the first 120 h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7–21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats. The identification of the periods during which 6mA epigenetic marks are put in place increases our understanding of this mammalian epigenetic modification, and raises the possibility that it may be associated with developmental processes.

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Evolution of Eukaryotic DNA Methylation and the Pursuit of Safer Sex

Current Biology ◽

10.1016/j.cub.2010.07.007 ◽

2010 ◽

Vol 20 (17) ◽

pp. R780-R785 ◽

Cited By ~ 100

Author(s):

Assaf Zemach ◽

Daniel Zilberman

Keyword(s):

Dna Methylation ◽

Safer Sex ◽

Eukaryotic Dna

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Prediction of CpG Islands as an Intrinsic Clustering Property Found in Many Eukaryotic DNA Sequences and Its Relation to DNA Methylation

Methods in Molecular Biology - CpG Islands ◽

10.1007/978-1-4939-7768-0_3 ◽

2018 ◽

pp. 31-47 ◽

Cited By ~ 2

Author(s):

Cristina Gómez-Martín ◽

Ricardo Lebrón ◽

José L. Oliver ◽

Michael Hackenberg

Keyword(s):

Dna Methylation ◽

Dna Sequences ◽

Cpg Islands ◽

Eukaryotic Dna ◽

Clustering Property

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Use of restriction enzymes to study eukaryotic DNA methylation

Journal of Molecular Biology ◽

10.1016/0022-2836(78)90242-5 ◽

1978 ◽

Vol 118 (1) ◽

pp. 27-47 ◽

Cited By ~ 237

Author(s):

Adrian P. Bird ◽

Edwin M. Southern

Keyword(s):

Dna Methylation ◽

Restriction Enzymes ◽

Eukaryotic Dna

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Extensive N4 Cytosine Methylation is Essential for Marchantia Sperm Function

10.1101/2021.02.12.428880 ◽

2021 ◽

Author(s):

James Walker ◽

Jingyi Zhang ◽

Yalin Liu ◽

Martin Vickers ◽

Liam Dolan ◽

...

Keyword(s):

Dna Methylation ◽

Cytosine Methylation ◽

Marchantia Polymorpha ◽

Sperm Function ◽

Dna Modification ◽

Entire Genome ◽

New Family ◽

Dna Modifications ◽

Eukaryotic Dna ◽

Second Wave

Abstract4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but its relevance, and even presence in eukaryotes have been mysterious. Here we show that spermatogenesis in the liverwort Marchantia polymorpha involves two waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC), a well-known eukaryotic DNA modification, expands from transposons to the entire genome. Notably, the second wave installs 4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC is catalyzed by two novel methyltransferases (MpDN4MT1a and MpDN4MT1b) specifically expressed during late spermiogenesis. Deletion of MpDN4MT1s eliminates 4mC, alters the sperm transcriptome, and produces sperm with swimming defects. Our results reveal extensive 4mC in a eukaryote and define a new family of eukaryotic methyltransferases, thereby expanding the repertoire of functional eukaryotic DNA modifications.

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