Mapping the epigenetic modifications of DNA and RNA
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Protein & Cell
REVIEW Mapping the epigenetic modifications of DNA and RNA Lin-Yong Zhao1,2,3
, Jinghui Song4,5, Yibin Liu2,3, Chun-Xiao Song2,3&
, Chengqi Yi
4,5,6&
Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China 2 Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK 3 Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK 4 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China 5 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China 6 Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China & Correspondence: [email protected] (C.-X. Song), [email protected] (C. Yi) Received February 12, 2020 Accepted March 16, 2020
ABSTRACT Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study. Here, we review the recent technological advances in this rapidly evolving field. We focus on high-throughput detection methods and biological findings for these modifications, and discuss questions to be addressed as well. We also summarize third-generation sequencing methods, which enable long-read and single-molecule sequencing of DNA and RNA modification.
KEYWORDS DNA modification, DNA methylation, RNA modification, epitranscriptomics, epigenetics, long read sequencing INTRODUCTION Mapping the epigenetic modifications of DNA and RNA becomes increasingly crucial to understand their diverse biological functions. At least 17 and 160 types of chemical
Lin-Yong Zhao and Jinghui Song have contributed equally to this work.
© The Author(s) 2020
modifications have been discovered in DNA and RNA, respectively (Raiber et al., 2017; Boccaletto et al., 2018). DNA modification plays important roles in several biological processes and diseases, including development (Greenberg and Bourc’his, 2019), aging (Unnikrishnan et al., 2019), cancer (Koch et al., 2018), etc. These modifications would not interfere with Watson-Crick pairing but affect the DNAprotein interaction while in the major groove of the double helix. In the mammalian genome, methylation at the 5th carbon of cytosine (5-methylcytosine, or 5mC) is the most predominant DNA modification, which is also called the “fifth base” (Greenberg and Bourc’his, 2019). The reaction is catalyzed by DNA methyltransferases (DNMTs) and mostly found in the context of symmetr
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