TY - JOUR
T1 - Critical assessment of DNA adenine methylation in eukaryotes using quantitative deconvolution
AU - Kong, Yimeng
AU - Cao, Lei
AU - Deikus, Gintaras
AU - Fan, Yu
AU - Mead, Edward A.
AU - Lai, Weiyi
AU - Zhang, Yizhou
AU - Yong, Raymund
AU - Sebra, Robert
AU - Wang, Hailin
AU - Zhang, Xue Song
AU - Fang, Gang
N1 - Funding Information:
Supported by the Icahn Institute for Genomics and Multiscale Biology, NIH grants R35 GM139655, R01 HG011095, and R56 AG071291, the Irma T. Hirschl/Monique Weill-Caulier Trust, and the Nash Family Foundation (G.F.). UHPLC-MS/MS analyses of 6mA were supported by Strategic Priority Research Program of the Chinese Academy of Sciences grant XDPB2004 and National Natural Science Foundation of China grant 22021003 (H.W.).
Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.
PY - 2022/2/4
Y1 - 2022/2/4
N2 - The discovery of N6-methyldeoxyadenine (6mA) across eukaryotes led to a search for additional epigenetic mechanisms. However, some studies have highlighted confounding factors that challenge the prevalence of 6mA in eukaryotes. We developed a metagenomic method to quantitatively deconvolve 6mA events from a genomic DNA sample into species of interest, genomic regions, and sources of contamination. Applying this method, we observed high-resolution 6mA deposition in two protozoa. We found that commensal or soil bacteria explained the vast majority of 6mA in insect and plant samples. We found no evidence of high abundance of 6mA in Drosophila, Arabidopsis, or humans. Plasmids used for genetic manipulation, even those from Dam methyltransferase mutant Escherichia coli, could carry abundant 6mA, confounding the evaluation of candidate 6mA methyltransferases and demethylases. On the basis of this work, we advocate for a reassessment of 6mA in eukaryotes.
AB - The discovery of N6-methyldeoxyadenine (6mA) across eukaryotes led to a search for additional epigenetic mechanisms. However, some studies have highlighted confounding factors that challenge the prevalence of 6mA in eukaryotes. We developed a metagenomic method to quantitatively deconvolve 6mA events from a genomic DNA sample into species of interest, genomic regions, and sources of contamination. Applying this method, we observed high-resolution 6mA deposition in two protozoa. We found that commensal or soil bacteria explained the vast majority of 6mA in insect and plant samples. We found no evidence of high abundance of 6mA in Drosophila, Arabidopsis, or humans. Plasmids used for genetic manipulation, even those from Dam methyltransferase mutant Escherichia coli, could carry abundant 6mA, confounding the evaluation of candidate 6mA methyltransferases and demethylases. On the basis of this work, we advocate for a reassessment of 6mA in eukaryotes.
UR - http://www.scopus.com/inward/record.url?scp=85123974586&partnerID=8YFLogxK
U2 - 10.1126/science.abe7489
DO - 10.1126/science.abe7489
M3 - Article
C2 - 35113693
AN - SCOPUS:85123974586
SN - 0036-8075
VL - 375
SP - 515
EP - 522
JO - Science
JF - Science
IS - 6580
M1 - A26
ER -