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Mol Cell. 2020 Jan 16;77(2):426-440.e6. doi: 10.1016/j.molcel.2019.09.032. Epub 2019 Oct 29.

Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues.

Author information

1
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
2
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
3
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai 200032, China; Human Phenome Institute, Fudan University, Shanghai 200032, China.
4
Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
5
University of Chinese Academy of Sciences, Beijing 100049, China.
6
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai 200032, China; Human Phenome Institute, Fudan University, Shanghai 200032, China. Electronic address: fan.jia@zs-hospital.sh.cn.
7
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China; Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: chengqi.yi@pku.edu.cn.

Abstract

N6-methyladenosine (m6A), the most abundant internal mRNA modification, and N6,2'-O-dimethyladenosine (m6Am), found at the first-transcribed nucleotide, are two reversible epitranscriptomic marks. However, the profiles and distribution patterns of m6A and m6Am across human and mouse tissues are poorly characterized. Here, we report the m6A and m6Am methylome through profiling of 43 human and 16 mouse tissues and demonstrate strongest tissue specificity for the brain tissues. A small subset of tissue-specific m6A peaks can also readily classify tissue types. The overall m6A and m6Am level is partially correlated with the expression level of their writers and erasers. Additionally, the m6A-containing regions are enriched for SNPs. Furthermore, cross-species analysis revealed that species rather than tissue type is the primary determinant of methylation. Collectively, our study provides an in-depth resource for dissecting the landscape and regulation of the m6A and m6Am epitranscriptomic marks across mammalian tissues.

KEYWORDS:

cross-species conservation; epitranscriptome analysis; m(6)A; m(6)Am; tissue specificity

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