Investigator, School of Life Sciences, Peking University
Investigator, Synthetic and Functional Biomolecules Center (SFBC)
Investigator, Peking-Tsinghua Center for Life Sciences.
Education and Research Background
Chengqi Yi, born in 1983 at Jinhua, China. Dr. Yi obtained his B.S. degree in Chemistry from University of Science and Technology of China in 2005 and his Ph.D. degree under the guidance of Prof. Chuan He at The University of Chicago in 2010. After a postdoctoral training with Prof. Tao Pan at The University of Chicago in 2010-2011, he moved back to China as an Investigator at Peking University since 2012. He has received many awards including the Chemistry Alumni Graduate Fellowship, The University of Chicago (2007) and IUPAC Prize for Young Chemists, International Union of Pure and Applied Chemistry (2011) and he was awarded by the Youth One Thousand People Plan in 2012.
Research Direction and Achievements
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.
1) Zhu, C.X., Lu, L.N., Zhang, J., Yue, Z.W., Song, J.H., Zong, S., Liu, M.H., Stovicek, O., Gao, Y.Q., and Yi, C.Q.* (2016). Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair. Proc. Natl. Acad. Sci. USA., 113, 7792-7797.
2) Li, X.Y., Xiong, X.S., Wang, K., Wang, L.X., Shu, X.T., Ma S.Q. and Yi, C.Q. * (2016). Transcriptome-wide mapping reveals reversible and dynamic N (1)-methyladenosine methylome. Nat. Chem. Biol., 12: 311-316.
3) Li, X.Y., Ma, S.Q. and Yi, C.Q. * (2016). Pseudouridine: the fifth RNA nucleotide with renewed interests. Curr. Opin. Chem. Biol., 33, 108-116.
4) Peng, J.Y., Xia, B. and Yi, C.Q. * (2016). Single-base resolution analysis of DNA epigenome via high-throughput sequencing. Sci. China Life Sci., 59, 219-226.
5) Xia, B., Han, D.L., Lu, X.Y., Sun, Z.Z., Zhou, A.K., Yin, Q.Z., Zeng, H., Liu, M.H., Jiang, X., Xie, W., He, C. and Yi C.Q. * (2015). Bisulfite-free, base-resolution analysis of 5-formylcytosine at the genome scale. Nat. Methods, 12, 1047-1050.
6) Li, X.Y., Zhu, P., Ma, S.Q., Song, J.H., Bai, J.Y., Sun, F.F. and Yi, C.Q. * (2015). Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nat. Chem. Biol., 11, 592-597.
7) Song, J.H., Zhu, C.X., Zhang, X., Wen, X., Liu, L.L., Peng, J.Y., Guo, H.W. and Yi, C.Q. * (2015). Biochemical and structural insights into the mechanism of DNA recognition by Arabidopsis ETHYLENE INSENSITIVE3. PLoS One, 10, e0137439.
8) Li, X.Y., Ma, S.Q. and Yi, C.Q. * (2015). Pseudouridine Chemical Labeling and Profiling. Methods Enzymol., 560, 247-272.
9) Karijolich, J., Yi, C.Q. and Yu, Y.T. (2015). Transcriptome-wide dynamics of RNA pseudouridylation. Nat. Rev. Mol. Cell Biol., 16, 581-585.
10) Zheng, G.Q., Qin, Y.D., Clark, W.C., Dai, Q., Yi, C.Q., He, C., Lambowitz, A.M. and Pan, T. (2015). Efficient and quantitative high-throughput tRNA sequencing. Nat. Methods. 12, 835-837.
11) Zhu, C.X. and Yi, C.Q. * (2014). Switching demethylation activities between AlkB family RNA/DNA demethylases through exchange of active-site residues. Angew. Chem. Int. Ed., 53, 3659-3662.
12) Lu, L.N., Zhu, C.X., Xia, B. and Yi, C.Q. * (2014). Oxidative demethylation of DNA and RNA mediated by non-heme iron-dependent dioxygenases. Chem. Asian. J., 9, 2018-2029.
13) Li, X.Y., Song J.H. and Yi, C.Q. * (2014). Genome-wide mapping of cellular protein-RNA interactions enabled by chemical crosslinking. Geno. Proteo. Bioinfor., 12, 72-78.
14) Yin, Y.D., Yang, L.J., Zheng G.Q., Gu, C., Yi, C.Q., He, C. Gao Y.Q. and Zhao, X.S. (2014). Dynamics of spontaneous flipping of a mismatched base in DNA duplex. Proc. Natl. Acad. Sci. USA., 111, 8043-8048.
15) Zhang, X., Zhu, Z.Q., An, F.Y., Hao, D.D., Li, P.99P., Song J.H., Yi, C.Q. and Guo, H.W. (2014). Jasmonate-activated MYC2 represses ETHYLENE INSENSITIVE3 activity to antagonize ethylene-promoted apical hook formation in Arabidopsis. Plant Cell, 26, 1105-1117.
16) Yi, C.Q. * and He, C. (2013). DNA repair by reversal of DNA damage. Cold Spring Harb. Perspect. Biol., 5, a0125.
17) Song, C.X., Yi, C.Q. and He, C. (2012). Mapping new nucleotide variants in the genome and transcriptome. Nat. Biotechnol., 30, 1107-1116.
18) Yi, C.Q., Chen, B.N., Zhang, W., Jia, G.F., Zhang, L., Li, C.J., Dinner, A.R., Yang, C.G. and He, C. (2012). Duplex interrogation by a direct DNA repair protein in search of base damage. Nat. Struct. Mol. Biol., 19, 671-676.