Quantifying propagation of DNA methylation and hydroxymethylation with iDEMS

被引：10
|
作者：
Stewart-Morgan, Kathleen R. [1 ,2 ]
Requena, Cristina E. [3 ,4 ]
Flury, Valentin [1 ,2 ]
Du, Qian [1 ,5 ,6 ]
Heckhausen, Zoe [3 ,4 ]
Hajkova, Petra [3 ,4 ]
Groth, Anja [1 ,2 ]
机构：
[1] Univ Copenhagen, Novo Nord Fdn Ctr Prot Res CPR, Fac Hlth & Med Sci, Copenhagen, Denmark
[2] Univ Copenhagen, Fac Hlth & Med Sci, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark
[3] MRC London Inst Med Sci LMS, London, England
[4] Imperial Coll London, Inst Clin Sci ICS, Fac Med, London, England
[5] Garvan Inst Med Res, Sydney, NSW, Australia
[6] Univ New South Wales, St Vincents Clin Sch, Sydney, NSW, Australia
来源：
NATURE CELL BIOLOGY | 2023年 / 25卷 / 01期
基金：
澳大利亚国家健康与医学研究理事会; 欧洲研究理事会; 欧盟地平线“2020”;
关键词：
CYTOSINE METHYLATION; 5-HYDROXYMETHYLCYTOSINE; REVEALS; DNMT1; MAINTENANCE; UHRF1; DEMETHYLATION; INHERITANCE; DOMAINS; 5HMC;
D O I：
10.1038/s41556-022-01048-x
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
DNA methylation is a critical epigenetic mark in mammalian cells. Many aspects of DNA methylation maintenance have been characterized; however, the exact kinetics of post-replicative methylation maintenance remain a subject of debate. Here we develop isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry (iDEMS), a highly sensitive, quantitative mass spectrometry-based method for measuring DNA modifications on metabolically labelled DNA. iDEMS reveals an unexpectedly hemi-methylated landscape on nascent DNA. Combining iDEMS with metabolic labelling reveals that methylation maintenance is outpaced by cell division in mouse embryonic stem cells. Our approach shows that hydroxymethylation is perpetually asymmetric between sister strands in favour of the parental, template strand. iDEMS can be coupled with immunoprecipitation of chromatin proteins, revealing features of DNA methylation-histone modification crosstalk and suggesting a model for interplay between methylation and nucleosome assembly. iDEMS therefore elucidates long-standing questions about DNA modification propagation and provides an important orthogonal technology to understanding this process in dynamic cellular contexts. Stewart-Morgan et al. present isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry, a highly sensitive, quantitative mass spectrometry-based method for measuring DNA modifications on metabolically labelled DNA. They apply it to study DNA methylation and hydroxymethylation propagation.
引用
收藏
页码：183 / +
页数：25
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