2005 – 2010, Ph.D. in Chemical Biology, University of Chicago
2001 – 2005, B.S. in Chemistry, University of Science and Technology of China
2014 – present, adjunct principle investigator, College of Chemistry and Molecular Engineering, Peking University
2013 – present, Principle Investigator, Synthetic and Functional Biomolecules Center (SFBC), Peking University
2012 – present, Principle Investigator, School of Life Sciences, Peking University
2012 – present, Principle Investigator, Center for Life Sciences
2010 – 2011, Postdoctoral fellow in Biochemistry & Molecular Biology, University of Chicago
Honors and Awards
National ten thousands plan program-leading talents in science and technology Innovation
The 16th Henry Fok Ying Tung Young Teachers Fund, 2018
Molecular Cell,Best of Molecular Cell，2017
Wang Xuan Young Scholar Award, 2017
The 10th `Yaoming Kangde Life Chemistry Research Award` scholar award, 2016
OKeanos-CAPA Young Investigator Award, 2018
Bayer Investigator at PKU, 2018
Chinese Chemical Society Chemical Biology Award, 2018
Chinese Chemical Society Youth Chemistry Award,2016
The National Science Fund for Distinguished Young Scholars, 2016
Luye Eminent Young Scholar Award, Peking University, 2014
Nation Youth 1000 Plan Program (The 2nd batch), 2012
IUPAC Prize for Young Chemists, International Union of Pure and Applied Chemistry, 2011
Chemistry Alumni Graduate Fellowship, University of Chicago, 2009-2010
Outstanding Student Scholarship, University of Science and Technology of China, 2003-2005
Zhang Zongzhi Sci-Tech Fellowship, University of Science and Technology of China, 2002
Professional Society Affiliations
2017 - present, the Chinese Cell Biology Society
2013 – present, the RNA society
2013 – present, the Chinese Society of Biochemistry and Molecular Biology
2012 – present, the Chinese Crystallographic Society
2012 – present, the Chinese Chemical Society
We probe the pathways and mechanisms of DNA/RNA modification and de-modification. In order to do so, we integrate multiple disciplines including chemical biology, epigenetics, nucleic acid chemistry, cell biology, biochemistry, genomics, and structural biology. An ultimate goal is to uncover new functions and regulatory mechanisms of the epigenetic DNA/RNA modifications.
1. RNA Modifications and EpitranscrIptomics
More than 100 distinct post-transcrIptional modifications have been characterized so far; they were considered to be static and unalterable after covalent installation. Recent discoveries of reversible RNA methylation in the form of N6-methyladenosine (m6A) have demonstrated RNA modification-mediated regulation of gene expression, leading to the emerging field of “epitranscrIptomics”.
In addition to m6A, there are other epitranscrIptomic marks. My laboratory recently discovered that pseudouridine (Ψ) and N1-methyladenosine (m1A), two post-transcrIptional modifications in non-coding RNAs, are also present in mammalian mRNAs. My laboratory showed that these epitranscrIptomic marks are prevalent in mRNA, dynamically-regulated by various stimuli and reversible by potential “eraser” proteins in the case of m1A. However, the biological consequences of mRNA pseudouridylation and m1A methylation are unknown. Utilizing epitranscrIptome sequencing tools we have developed, we hope to elucidate the functional consequences and regulatory mechanisms of these RNA modifications, hence leading to new territories in the nascent field of epitranscrIptomics.
2. TET- and TDG-dependent Active DNA Demethylation
The ten-eleven translocation (TET)-dependent generation and removal of oxidized derivatives of 5-methylcytosine (5mC), namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), uncovered a new paradigm of active DNA demethylation in mammalian genomes. Besides acting as demethylation intermediates, these oxidized variants of 5mC may also play functional roles. Emerging evidence has suggested 5hmC as a stable epigenetic modification implicated in many biological processes and various diseases. 5fC and 5caC, further oxidation products of 5hmC, accumulate at distal regulatory elements as active DNA demethylation intermediates and can be removed through base excision repair by mammalian thymine DNA glycosylase (TDG). My laboratory recently developed “fC-CET”, a bisulfite-free, base-resolution method for the genome-wide identification of 5fC sites. We will continue to develop robust and sensitive sequencing technologies, including those applicable to single-cell studies and clinical investigations, to dissect the functional roles of these epigenetic DNA modifications.
3. DNA Repair and Protein-DNA Interactions
Aberrant modification to DNA can lead to cytotoxic or mutagenic consequences. Once damaged, cellular DNA must be promptly repaired. Organisms have evolved a variety of mechanisms to repair these cytotoxic or mutagenic damages; in the Yi Group, we are interested in the base-excision repair and direct repair pathways. One component of our research is to utilize a novel chemical cross-linking technique to stabilize protein-DNA interactions in these systems. For instance, my group recently revealed an unprecedented mechanism of DNA repair glycosylase hNEIL1: it promotes tautomerization of thymine glycol-a preferred substrate-for efficient substrate recognition and excision. An integrative approach uniting chemical synthesis, structural biology and biochemical/biophysical characterization is used to study these interactions in DNA/RNA base repair and modification proteins.
Representative Peer-Reviewed Publications
1. Zeng H, Mondal M, Song R, Zhang J, Xia B, Liu M, Zhu C, He B, Gao Y*, Yi C*. Unnatural Cytosine Bases Recognized as Thymines by DNA Polymerases by the Formation of the Watson-Crick Geometry. Angew. Chem. Int. Edit. 2019; 58: 130-133.
2. Sun H, Zhang M, Li K, Bai D, Yi C*. Cap-specific, terminal N(6)-methylation by a mammalian m(6)Am methyltransferase. Cell Res. 2019; 29: 80-82.
3. Wang K, Yi C*. Coupling Transcription and Translation via the Epitranscriptomic m(6)A Mark. Biochemistry. 2019; 58: 297-298.
4. Zeng H, He B, Yi C*. Compilation of modern technologies to map genome-wide cytosine modifications in DNA. Chem. Bio. Chem. 2019.
5. Shu X, Liu M, Lu Z, Zhu C, Meng H, Huang S, Zhang X, Yi C*. Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA. Nat. Chem. Biol. 2018; 14: 680-687.
6. Xiong X, Li X, Wang K, Yi C*. Perspectives on topology of the human m(1)A methylome at single nucleotide resolution. RNA. 2018; 24: 1437-1442.
7. Xiong X, Li X, Yi C*. N(1)-methyladenosine methylome in messenger RNA and non-coding RNA. Curr. Opin. Chem. Biol. 2018; 45: 179-186.
8. Zeng H, He B, Xia B, Bai D, Lu X, Cai J, Chen L, Zhou A, Zhu C, Meng H, Gao Y, Guo H, He C*, Dai Q* Yi C*. Bisulfite-Free, Nanoscale Analysis of 5-Hydroxymethylcytosine at Single Base Resolution. J. Am. Chem. Soc. 2018; 140: 13190-13194.
9. Zeng H, He B, Yi C*, Peng J*. Liquid biopsies: DNA methylation analyses in circulating cell-free DNA. J. Genet. Genomics. 2018; 45: 185-192.
10. Li X, Xiong X, Zhang M, Wang K, Chen Y, Zhou J, Mao Y, Lv J, Yi D, Chen X, Wang C, Qian S, Yi C*. Base-Resolution Mapping Reveals Distinct m1A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts. Molecular Cell, 2017; 68: 993-1005.
11. Zhu C, Gao Y, Guo H, Xia B, Song J, Wu X, Zeng H, Kee K, Tang F*, Yi C*. Single-Cell 5-Formylcytosine Landscapes of Mammalian Early Embryos and ESCs at Single-Base Resolution. Cell Stem Cell, 2017; 20: 720-731.
12. Zhang Y, Liu L, Guo S, Song J, Zhu C, Yue Z, Wei W*, Yi C*. Deciphering TAL effectors for 5-methylcytosine and 5-hydroxymethylcytosine recognition. Nat. Commun., 2017; 8: 901.
13. Lei Z, Yi C*. A Radiolabeling-Free, qPCR-Based Method for Locus-Specific Pseudouridine Detection. Angew. Chem. Int. Ed. Engl., 2017; 56: 14878-14882.
14. Li X, Xiong X, Yi C*. Epitranscriptome sequencing technologies: decoding RNA modifications. Nat. Methods, 2016; 14: 23-31.
15. Li X, Xiong X, Wang K, Wang L, Shu X, Ma S, Yi C*. Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome. Nat. Chem. Biol., 2016; 12: 311-316.
16. Zhu C, Lu L, Zhang J, Yue Z, Song J, Zong S, Liu M, Stovicek O, Gao Y*, Yi C*. Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair. Proc. Natl. Acad. Sci. USA., 2016; 113: 7792-7797.
17. Shu X, Xiong X, Song J, He C*, Yi C*. Base-Resolution Analysis of Cisplatin-DNA Adducts at the Genome Scale. Angew. Chem. Int. Ed. Engl., 2016; 55: 14246-14249.
18. Li X, Zhu P, Ma S, Song J, Bai J, Sun F, Yi C*. Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nat. Chem. Biol., 2015; 11: 592-597.
19. Xia B, Han D, Lu X, Sun Z, Zhou A, Yin Q, Zeng H, Liu M, Jiang X, Xie W, He C*, Yi C*. Bisulfite-free, base-resolution analysis of 5-formylcytosine at the genome scale. Nat. Methods, 2015; 12: 1047-1050.
We probe the pathways and mechanisms of DNA/RNA
modification and de-modification. In order to do so, we integrate multiple
disciplines including chemical biology, epigenetics, nucleic acid chemistry,
cell biology, biochemistry, genomics, and structural biology. An ultimate goal
is to uncover new functions and regulatory mechanisms of the epigenetic DNA/RNA