Critical assessment of DNA adenine methylation in eukaryotes using quantitative deconvolution

Kong, Yawei; Cao, Lei; Deikus, Gintaras; Yu, Fan; Mead, Edward A.; Lai, Weiyi; Zhang, Yizhou; Yong, Raymund L.; Sebra, Robert; Wang, Hailin; Zhang, Xue Song; Fang, Gang

doi:10.1126/science.abe7489

Cited by 85 publications

(109 citation statements)

References 57 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…DNA methylation is an important epigenetic modification that plays crucial roles in a variety of cellular processes, such as gene regulation, animal development, X-chromosome inactivation, and chromatin organization 1 – 4 . Methylation of N6-adenine (6 mA) on DNA was recently discovered to be present in diverse eukaryotes, though it exists at low levels in most of these organisms 5 – 10 . Unlike the well-studied C5-cytosine methylation (5 mC), the biological functions of 6 mA in eukaryotic genomic DNA is complicated and the various epigenetic mechanisms related to 6 mA remain to be further investigated 11 .…”

Section: Introductionmentioning

confidence: 99%

Structural basis for MTA1c-mediated DNA N6-adenine methylation

Chen

et al. 2022

Nat Commun

View full text Add to dashboard Cite

DNA N6-adenine methylation (6 mA) has recently been found to play a crucial role in epigenetic regulation in eukaryotes. MTA1c, a newly discovered 6 mA methyltransferase complex in ciliates, is composed of MTA1, MTA9, p1 and p2 subunits and specifically methylates ApT dinucleotides, yet its mechanism of action remains unknown. Here, we report the structures of Tetrahymena thermophila MTA1 (TthMTA1), Paramecium tetraurelia MTA9 (PteMTA9)-TthMTA1 binary complex, as well as the structures of TthMTA1-p1-p2 and TthMTA1-p2 complexes in apo, S-adenosyl methionine-bound and S-adenosyl homocysteine-bound states. We show that MTA1 is the catalytically active subunit, p1 and p2 are involved in the formation of substrate DNA-binding channel, and MTA9 plays a structural role in the stabilization of substrate binding. We identify that MTA1 is a cofactor-dependent catalytically active subunit, which exhibits stable SAM-binding activity only after assembly with p2. Our structures and corresponding functional studies provide a more detailed mechanistic understanding of 6 mA methylation.

show abstract

Section: Introductionmentioning

confidence: 99%

Structural basis for MTA1c-mediated DNA N6-adenine methylation

Chen

et al. 2022

Nat Commun

View full text Add to dashboard Cite

show abstract

“…(CI, 1-13 p.p.m.) by 6mASCOPE in the two glioblastoma species, suggesting that the 6 mA level in human cells might be overestimated (Kong et al, 2022). Zhang et al 2022b.…”

Section: Prevalence Of 6 Mamentioning

confidence: 93%

“…et al, 2018b). However, 6mASCOPE showed that the 6 mA/A level of VATN sites was 2-3 times higher than that of NATN sites (Kong et al, 2022). Compared to protozoans and metazoans, 6 mA has been less researched in plants and fungi.…”

Section: Prevalence Of 6 Mamentioning

confidence: 95%

“…(CI, 1-10 p.p.m.) suggesting that previous measurements could be affected by bacterial contamination (Kong et al, 2022). In Bdelloid rotifer, 6 mA existed on 17,886 adenines (0.0236% of total adenines) (Rodriguez et al, 2022).…”

Section: Prevalence Of 6 Mamentioning

confidence: 97%

“…reported that the level of 6 mA was up to 0.048% (6 mA/A) by LC-MS/MS. Kong et al (2022). quantified the 6 mA/A level in 21-day-old Arabidopsis seedlings (approximately 2,500 p.p.m.…”

Section: Prevalence Of 6 Mamentioning

confidence: 99%

See 2 more Smart Citations

DNA N6-Methyladenine Modification in Eukaryotic Genome

Zhang

Wang

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

DNA methylation is treated as an important epigenetic mark in various biological activities. In the past, a large number of articles focused on 5 mC while lacking attention to N6-methyladenine (6 mA). The presence of 6 mA modification was previously discovered only in prokaryotes. Recently, with the development of detection technologies, 6 mA has been found in several eukaryotes, including protozoans, metazoans, plants, and fungi. The importance of 6 mA in prokaryotes and single-celled eukaryotes has been widely accepted. However, due to the incredibly low density of 6 mA and restrictions on detection technologies, the prevalence of 6 mA and its role in biological processes in eukaryotic organisms are highly debated. In this review, we first summarize the advantages and disadvantages of 6 mA detection methods. Then, we conclude existing reports on the prevalence of 6 mA in eukaryotic organisms. Next, we highlight possible methyltransferases, demethylases, and the recognition proteins of 6 mA. In addition, we summarize the functions of 6 mA in eukaryotes. Last but not least, we summarize our point of view and put forward the problems that need further research.

show abstract

Artificial Intelligence‐Assisted Label‐Free Spectroscopic Quantification of Global DNA Cytosine Methylation in a Miniature Plasmonic Pickering Emulsion

Xie,

Chen,

Liu

et al. 2023

Adv Funct Materials

View full text Add to dashboard Cite

Epigenetic DNA methylations are early and frequently observed events in a diversity of diseases such as cancer. Despite the considerable clinical values for cancer liquid biopsy, quantitative analysis of DNA methylations remains a major challenge due to the lack of rapid, sensitive detection techniques. Here, an artificial intelligence‐assisted label‐free surface‐enhanced Raman spectroscopy (SERS) (iMeSERS) biosensor is reported for simultaneous quantification of C5‐methylcytosine (5mC) level and methylation ratio in DNA samples. This method utilizes the plasmonic Pickering emulsions as the biosensing platform for label‐free SERS detection, formed upon the addition of a sub‐microliter DNA sample to the hydrophobic Au nanostar‐containing n‐decane. Distinct spectral signatures of monophosphates of canonical deoxyribonucleotides (dNMPs) and the common methylation modification 5‐methyl‐2′‐deoxycytidine (d5mCMP) are identified and distinguished by the iMeSERS biosensor. The deep learning algorithms trained with SERS signatures of dNMPs and d5mCMP are then applied to the quantitative analysis of global DNA methylation. The exceptional capability of the deep learning‐driven approach is demonstrated for simultaneous quantification of the methylation ratio and level using a sub‐microliter volume of DNA samples. This work shows the power of label‐free SERS techniques combined with deep learning algorithms for quantitative analysis of epigenetic DNA modifications with great promises for clinical diagnosis.

show abstract

Critical assessment of DNA adenine methylation in eukaryotes using quantitative deconvolution

Cited by 85 publications

References 57 publications

Structural basis for MTA1c-mediated DNA N6-adenine methylation

Structural basis for MTA1c-mediated DNA N6-adenine methylation

DNA N6-Methyladenine Modification in Eukaryotic Genome

Artificial Intelligence‐Assisted Label‐Free Spectroscopic Quantification of Global DNA Cytosine Methylation in a Miniature Plasmonic Pickering Emulsion

Contact Info

Product

Resources

About