bioRxiv preprint doi: https://doi.org/10.1101/632000; this version posted May 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
1 Landscape and regulation of m6A and m6Am methylome
2 across human and mouse tissues
3 Jun’e Liu1,#, Kai Li1,2,3,#, Jiabin Cai5,6,#, Mingchang Zhang7,#, Xiaoting Zhang1, 4 Xushen Xiong1,2,3, Haowei Meng1, Xizhan Xu8, Zhibin Huang7, Jia Fan5,6,* & 5 Chengqi Yi1,2,4,*
6 1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences,
7 Peking University, Beijing 100871, China.
8 2Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871,
9 China
10 3Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
11 4Department of Chemical Biology and Synthetic and Functional Biomolecules Center,
12 College of Chemistry and Molecular Engineering, Peking University, Beijing 100871,
13 China.
14 5Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan
15 Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of
16 Ministry of Education, Shanghai, 200032, China
17 6Human Phenome Institute, Fudan University, Shanghai, 200032, China
18 7Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University,
19 Shanghai 200032, China
20 8CAS Key Laboratory for Pathogenic Microbiology and Immunology, Institute of
21 Microbiology, Chinese Academy of Sciences, Beijing 100101, China
22 #These authors contributed equally to this work.
23 *Correspondence: [email protected] (J. F.); [email protected] (C. Y.)
24
1 bioRxiv preprint doi: https://doi.org/10.1101/632000; this version posted May 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
1 SUMMARY
2 N6-methyladenosine (m6A), the most abundant internal mRNA modification,
3 and N6,2’-O-dimethyladenosine (m6Am), found at the first-transcribed
4 nucleotide, are two examples of dynamic and reversible epitranscriptomic
5 marks. However, the profiles and distribution patterns of m6A and m6Am
6 across different human and mouse tissues are poorly characterized. Here we
7 report the m6A and m6Am methylome through an extensive profiling of 42
8 human tissues and 16 mouse tissue samples. Globally, the m6A and m6Am
9 peaks in non-brain tissues demonstrates mild tissue-specificity but are
10 correlated in general, whereas the m6A and m6Am methylomes of brain tissues
11 are clearly resolved from the non-brain tissues. Nevertheless, we identified a
12 small subset of tissue-specific m6A peaks that can readily classify the tissue
13 types. The number of m6A and m6Am peaks are partially correlated with the
14 expression levels of their writers and erasers. In addition, the m6A- and
15 m6Am-containing regions are enriched for single nucleotide polymorphisms.
16 Furthermore, cross-species analysis of m6A and m6Am methylomes revealed
17 that species, rather than tissue types, is the primary determinant of methylation.
18 Collectively, our study provides an in-depth resource for dissecting the
19 landscape and regulation of the m6A and m6Am epitranscriptomic marks
20 across mammalian tissues.
21
2 bioRxiv preprint doi: https://doi.org/10.1101/632000; this version posted May 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
1 INTRODUCTION
2 More than 100 RNA modifications have been characterized so