Haitao Li-School of Medicine, Tsinghua University

Cell and Molecular Biology

Haitao Li

Contact Us:
Tel: +86-10-62771392
E-mail: lht@tsinghua.edu.cn
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1993-1997 Department of Microbiology, Shandong University BSc

1997-2003 Institute of Biophysics, Chinese Academy of Sciences PhD

2003-2010 Memorial Sloan-Kettering Cancer Center Research Fellow (10/2003),

Research Associate (8/2005), and Senior Research Scientist (11/2006)

2010-2016 School of Medicine, Tsinghua University Associate Professor

2016-present School of Medicine, Tsinghua University Professor


My research is directed toward a molecular understanding of epigenetic regulation. Epigenetics concerns the process that our genetic information is organized and decoded at the chromosomal level. Epigenetic mechanisms include chemical modifications to histones or DNA/RNA, histone variants, chromatin remodeling, and non-coding RNAs. Epigenetics plays a key role in many biological processes, ranging from gene regulation to cell fate decision. Meanwhile, growing evidence shows that epigenetic dysregulation can give rise to diverse human diseases, notably cancer. We mainly apply structural biology blended with biochemical, chemical biological, and cell biological approaches to study key molecular recognition and catalysis events in epigenetics and modification biology. Other endeavors in the lab include structure-guided molecular engineering and drug discovery.

Honors and Awards:

➢2019 Young Scholar of China Award in Cancer Research

➢2019 Promega Innovation Awards for Cell Biology

➢2017 NSF Distinguished Young Scholars of China

➢2016 The 15thOutstandingMentor Award,Tsinghua University

➢2015MOEChang JiangYoungScholar

➢2015 The 9thAnnual Wuxi PharmaTech Life Science and Chemistry Awards

➢2015 HFSP Young Investigators Grant Award

➢2014 The 17thMao Yi-sheng Science and Technology Award for Beijing Youth

➢2013 Tsinghua Young Scholar of Distinction

➢2012 MOE New Century Excellent Talents in University

Editorial Board:

2020-presentHereditas(Beijing) Associate Editor


2018-presentClinical Epigenetics

2015-presentSignal Transduction and Targeted Therapy


Research Articles

1.Zhao S, Chuh KN, Zhang B, Dul BE, Thomson RE, Farrelly LA, Liu X, Xu N, Xue Y, Roeder RG, Maze I*, Muir TW*, andLi H*(2021) Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout.Proc Natl Acad Sci USA(https://doi.org/10.1073/pnas.2016742118)

2.Ren X, Zhao Y, Xue Z, Hao N, Li Y, Guo X, Wang D, Shi X, andLi H*(2021) Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins.Nucleic Acids Res49: 114-126

3.Jiang Y, Chen G, Li XM, Liu S, Tian G, Li Y*, Li X*,Li H*and Li XD*(2020) Selective targeting of AF9 YEATS domain by cyclopeptide inhibitors with preorganized conformation.J Am Chem Soc142: 21450–21459

4.Zhao F, Liu Y, Su X, Lee JE, Song Y, Wang D, Ge K, Gao J, Zhang MQ, andLi H*(2020) Molecular basis for histone H3 “K4me3-K9me3/2” methylation pattern readout by Spindlin1.J Biol Chem295: 16877-16887

5.Armache A, Yang S, Eobbins LE, Durmaz C, Daman AW, Jeong JQ, Marinez de Paz A, Ravishankar A, Arslan T, Lin S, Panchenko T, Garcia BA, Hake SB, Allis CD,Li H*, and Josefowicz SZ* (2020) Histone H3.3 phosphorylation amplifies stimulation-induced transcription.Nature583: 852–857

6.Li Z, Zhao S, Nelakanti RV, Lin K, Wu TP, Alderman III MH, Guo C, Wang P, Zhang M, Min W, Jiang Z, Wang Y,Li H*, Xiao A* (2020)N6-methyladenine in DNA antagonizes chromatin organizer SATB1 in early development.Nature583: 625–630

7.Zhang M, Yang S, Nelakanti R, Zhao W, Liu G, Li Z, Liu X, Wu T, Xiao A*, andLi H*(2020) Mammalian ALKBH1 serves as anN6-mA demethylase of unpairing DNA.Cell Res30: 197-210

8.Zheng Y, Zhang X, andLi H*(2020) Molecular basis for histidine N3-specific methylation of actin His73 by SETD3.Cell Disc6, 3

9.Wang L, Gao Y, Zheng X, Liu C, Dong S, Li R, Zhang G, Wei Y, Qu H, Li Y, Allis CD, Li G,Li H*, and Li P* (2019) Histone modifications regulate chromatin compartmentalization by contributing to a phase separation mechanism.Mol Cell76: 646-659

10.Weinberg DN, Papillon-Cavanagh S, Chen H, Yue Y, Chen X, Rajagopalan KN, Horth C, McGuire JT, Xu X, Nikbakht H, Lemiesz AE, Marchione DM, Marunde MR, Meiners MJ, Cheek MA, Keogh MC, Bareke E, Djedid A, Harutyunyan AS, Jabado N, Garcia BA,Li H, Allis CD, Majewski J, and Lu C (2019) The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape.Nature573: 281-286

11.Zhang X, Cao R, Niu J, Yang S, Ma H, Zhao S, andLi H*(2019) Molecular basis for hierarchical histone de-β-hydroxybutyrylation by SIRT3.Cell Disc5:35

12.Liu G, Zheng X, Guan H, Cao Y, Qu H, Kang J, Ren X, Lei J, Dong M, Li X, andLi H*(2019) Architecture of Saccharomyces cerevisiae SAGA complex.Cell Disc5:25

13.Farrelly LA, Thompson RE, Zhao S, Lepack AE, Lyu Y, Bhanu NV, Zhang B, Loh YE, Ramakrishnan A, Vadodaria KC, Heard KJ, Erikson G, Nakadai T, Bastle RM, Lukasak BJ, Zebroski H 3rd, Alenina N, Bader M, Berton O, Roeder RG, Molina H, Gage FH, Shen L, Garcia BA,Li H, Muir TW, and Maze I*(2019) Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3.Nature567: 535-539

14.Mariappan A, Soni K, Schorpp K, Zhao F, Minakar A, Zheng X, Mandad S, Macheleidt I, Ramani A, Kubelka T, Dawidowski M, Golfmann K, Wason A, Yang C, Simons, J, Schmalz, HG, Hyman AA, Aneja R, Ullrich R, Urlaub H, Odenthal M, Buttner R,Li H, Sattler M, Hadian K, and Gopalakrishnan J* (2019) Inhibition of CPAP–tubulin interaction prevents proliferation of centrosome-amplified cancer cells.EMBO J38: e99876

15.Zhao S, Cheng L, Gao Y, Zhang B, Zheng X, Wang L, Li P*, Sun Q*, andLi H*(2019) Plant HP1 protein ADCP1 links multivalent H3K9 methylation readout to heterochromatin formation.Cell Res29:54-66

16.Li X, Li XM, Jiang Y, Liu Z, Cui Y, Fung KY, van der Beelen She, Tian G, Wang L, Shi X, Allis CD,Li H, Li Y*, Li XD*(2018) Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking.Nat Chem Biol14:1140-1149

17.Klein BJ, Vann KR, Andrews FH, Wang WW, Zhang J, Zhang Y, Beloglazkina AA, Mi W, Li Y,Li H, Shi X, Kutateladze AG, Strahl BD, Liu WR, and Kutateladze TG* (2018) Structural insights into the π-π-π stacking mechanism and DNA-binding activity of the YEATS domain.Nat Commun9:4574

18.Fang J, Huang Y, Mao G, Yang S, Rennert G, Gu, L,Li H, and Li GM* (2018) Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3–MutSα interaction.Proc Natl Acad Sci USA115: 9598-9603

19.Guo J, Zhao F, Yin W, Zhu M, Hao C, Pang Y, Wu T, Wang J, Zhao D*,Li H*, and Cheng M* (2018) Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors.EurJ Med Chem155: 197-209

20.Hsu C, Zhao D, Shi J, Peng D, Guan H, Li Y, Huang Y, Wen H, Li W*,Li H*, and Shi X* (2018) Gas41 links histone acetylation to H2A.Z deposition and maintenance of embryonic stem cell identity.Cell Discovery4, 28

21.Cao R, Zhang X, Liu X, Li Y, andLi H* (2018) Molecular basis for histidine N1 position-specific methylation by CARNMT1.Cell Res28: 494-496

22.Hsu C, Shi J, Yuan C, Zhao D, Jiang S, Lyu J, Wang X,Li H, Wen H, Li W, and Shi X (2018) Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition in non-small cell lung cancer.Genes Dev, 32: 58-69

23.Zhao S, Zhang B, Yang M, Zhu J, andLi H*(2018) Systematic profiling of histone readers inArabidopsis thaliana.Cell Reports22: 1090-1102

24.Hao C, Zhao F, Song HY, Guo J, Li X, Jiang X, Huang R, Song S, Zhang Q, Wang R, Wang K, Pang Y, Liu T, Lu T, Huang W, Wang J, Lin B, He Z,Li H*, Li F*, Zhao D*, and Cheng M* (2018) Structure-based design of 6-chloro-4-aminoquinazoline-2-carboxamide derivatives as potent and selective p21-activated kinase 4 (PAK4) inhibitors.J Med Chem61: 265-285

25.Mi W, Guan H, Lyu J, Zhao D, Xi Y, Jiang S, Andrews FH, Wang X, Gagea M, Wen H, Tora L, Dent SYR, Kutateladze TG, Li W*,Li H*, and Shi X* (2017)YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer.Nat Commun8:1088

26.Li Z, Zhao D, Xiang B, andLi H*(2017)Structural and biochemical characterization of DAXX-ATRX interaction.Protein Cell8: 762-766

27.Zhao S, Yang M, Zhou W, Zhang B, Cheng Z, Huang J. Zhang M, Wang Z, Wang R, Chen Z, Zhu J*, andLi H*(2017) Kinetic and high-throughput profiling of epigenetic interactions by 3D-carbene chip-based surface plasmon resonance imaging technology.Proc Natl Acad Sci USA114: E7245-E7254

28.Bae N, Viviano M, Su X, Lyu J, Cheng D, Sagum C, Castellano S, Bai X, Johnson C, Khalil ML, Shen J, Chen K,Li H*, Sbardella G*, and Bedford MT* (2017) Developing Spindlin1 small molecule inhibitors using protein microarrays.Nat Chem Biol13:750-756

29.Wan L, Wen H, Li Y, Lvu J, Xi Y, Hoshii T, Joseph J, Wang X, Loh Y, Erb MA, Souza AL, Bradner JE, Shen L, Li W,Li H#, Allis CD#*, Armstrong SA#*, and Shi X#* (2017) ENL links histone acetylation to oncogenic gene expression in AML.Nature543, 265-269 (#co-senior author)

30.Xiong X, Panchenko T, Yang S, Zhao S, Yan P, Zhang W, Xie W, Li Y, Zhao Y, Allis CD, andLi H*(2016) Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.Nat Chem Biol12:1111-1118

31.Yang S, Zheng X, Lu C, Li G-M, Allis CD, andLi H* (2016) Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase.Genes Dev30:1611-1616

32.Li N, Li Y, Chen K, Zheng X, Shen H, Wen H, Chen T. Dhar SS, Kan P, Zhu G, Wang Z, Shi X, Lan F, Li W*,Li H*and Lee MG* (2016) ZMYND8 complexes with JARID1D to read a poised histone H3K4me1-H3K14ac signature for metastasis-linked gene repression.Mol Cell63:470-484

33.Zheng X, Ramani A, Soni K, Gottardo M, Zheng S, Ming Gooi L, Li W, Feng S, Mariappan A, Wason A, Wildlund P, Pozniakovaky A, Poser I, Deng H, Ou G, Riparbelli MG, Callaini G, Sattler M, Hyman A, Gopalakrishnan J*,Li H*(2016) Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length.Nat Commun7:11874

34.Zhang X, Zhao D, Xiong X,He Z,andLi H*(2016) Multifaceted histone H3 methylation andphosphorylation readout by the plant homeodomain (PHD) finger of human nuclear antigen Sp100C.J Biol Chem291:12786-12798

35.Zhao D, Guan H, Zhao S, Mi W, Wen H, Li Y, Zhao Y, Allis CD, Shi X*, andLi H*(2016) YEATS2 is a selective histone crotonylation reader.Cell Research26:629–632

36.Li Y, Sabari BR, Panchenko T, Wen H, Zhao D, Guan H, Wan L, Tang Z, Zhao Y, Roeder R. Shi X, Allis CD*, andLi H*(2016) Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain.Mol Cell62:181-193

37.Zhao D, Zhang X, Guan H, Xiong X, Shi Xi, Deng H, andLi H*(2016) The BAH domain of BAHD1 is a histone H3K27me3 reader.Protein Cell7: 222-226

38.Wu R, Yue Y, Zheng X, andLi H*(2015) Molecular basis for histone N-terminal methylation by NRMT1.Genes Dev29:2337-2342

39.Kamps J, Huang J, Poater J, Xu C, Pieters B, Dong A, Min J, Sherman W, Beuming T, Bickelhaupt FM,Li H, and Mecinovic J*(2015) Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins.Nat Commun6: 8911

40.Noh K, Wang H, Kim HR, Wenderski W, Fang F, Li CH, Dewell S, Hughes SH, Melnick AM, Patel DJ,Li H*, and Allis CD* (2015) Engineering of a histone-recognition domain in Dntm3a alters the epigenetic landscape and phenotypic features of mouse ESCs.Mol Cell59:89-103

41.Noh K, Maze I, Zhao D, Xiang B, Wenderski W, Lewis PW, Shen L,Li H*and Allis CD* (2015) ATRX tolerates activity-dependent histone H3 "methyl/phos switching" to maintain repetitive element silencing in neurons.Proc Natl Acad Sci USA112(22): 6820-6827

42.Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SYR, Li W,Li H*, and Shi X* (2014) AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation.Cell159:558-571

43.Wen H*, Li, Y, Xi Y, Jiang S, Stratton S, Peng D, Tanaka K, Ren Y, Xia Z, Wu J, Li B, Barton MC, Li W*,Li H*, and Shi X* (2014) ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression.Nature507, 263-268

44.Su X, Zhu G, Ding X, Lee SY, Dou Y, Zhu B, Wu W*, andLi H*(2014) Molecular basis underlying histone H3 lysine-arginine methylation patter readout by Spin/Ssty repeats of Spindlin1.Genes Dev28:622-636

45.Zheng X, Gooi, LM, Wason A, Gabriel E, Mehrjardi NZ, Yang Q, Zhang X, Debec A, Basiri M, Avidor-Reiss T, Pozniakovsky A, Poser I, Saric T, Hyman AA,Li H*and Gopalakrishnan J* (2014) The conserved TCP domain of Sas-4/CPAP is essential for Peri-centriolar material tethering during centrosome biogenesis.Proc Natl Acad Sci USA111: E345-E363

46.Ratnakumar K, Duarte LF, LeRoy G, Hasson D, Smeets D, Vardabasso C, Bönisch C, Zeng T, Xiang B, Zhang DY,Li H, Wang X, Hake SB, Schermelleh L, Garcia BA, Bernstein E (2012) ATRX-mediated chromatin association of histone variant macroH2A1 regulates alpha globin expression.Gene & Dev26(5): 433-438

47.Iwase S, Xiang B, Ghosh S, Ren T, Lewis PW, Cochrane JC, Allis CD, Picketts DJ, Patel DJ*,Li H*, Shi Y* (2011) ATRX links atypical histone methylation recognition mechanisms to human mental retardation syndrome.Nat Struct Mol Biol18: 769-776

48.Ruthenburg AJ,Li H, Milne T, Dou Y, McGinty RK, Yuen M, Muir TW, Patel DJ and Allis CD (2011) Recognition of a Mononucleosomal Histone Modification Pattern by BPTF via Multivalent Interactions.Cell145: 692-706

49.Wang Z, Song J, Tom M, Wang GG,Li H, Allis CD and Patel DJ (2010) Pro Isomerization in MLL1 PHD3-Bromo Cassette Connects H3K4me Readout to CyP33 and HDAC-Mediated Repression.Cell141:1183-94

50.Xiao A,Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ and Allis CD. (2009) WSTF regulates the DNA damage response of H2A.X via a novel tyrosine kinase activity.Nature457, 57-62

51.Wang GG, Song J, Wang Z, Dormann HL, Casadio F,Li H, Luo J, Patel DJ and Allis CD (2009) Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.Nature459, 847-851

52.Wang Y, Juranek S,Li H, Sheng G, Greg SW, Tuschl T and Patel DJ (2009) Nucleation, propagation and cleavage of target RNAs in argonaute silencing complexes.Nature461:754-61

53.Li H#, Motamedi MR#, Yip CK, Wang Z, Walz T, Patel DJ and Moazed D (2009) An alpha motif at Tas3 C terminus mediates RITS cis-spreading and promotes heterochromatic gene silencing.Mol Cell34(2), 155-167 (#equal contribution)

54.Wang Y, Juranek S,Li H, Sheng G, Tuschl T and Patel DJ (2008) Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex.Nature456, 921-926

55.Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, and Patel DJ (2007) Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger.Mol Cell28, 677-691

56.Li H, Ilin S, Wang W, Duncan EM, Wysocka J, Allis, CD, and Patel DJ (2006) Molecular basis for site-specific readout of histone H3K4 trimethylation by the BPTF PHD finger of NURF.Nature442, 91-95

Invited Reviews& Book Chapters

1.Zhang M andLi H*(2021)Missing for partnership: understanding nucleosomal de novo DNA cytosine methylation by a spliced DNMT3 complex.Signal Transduct Target Ther,(https://doi.org/10.1038/s41392-021-00461-2)

2.Zhao S, Yue Y, Li Y andLi H*(2019) Identification and characterization of ‘readers’ for novel histone modifications.Curr Opin Chem Biol, 51:57-65

3.Zhao S, Zhang X, andLi H*(2018) Beyond histone acetylation – writing and erasing histone acylationsCurr Opin Struc Biol, 53:169–177

4.Zhao S, Li Y, andLi H* (2018) Chemical and biological foundations of histone modification. In:Zhu JD (eds)Epigenetics and Precision Medicine:132-157 Shanghai Jiaotong University Press (Chapter 5, in Chinese,ISBN 9787313184115)

5.Zhao D, Li Y, Xiong X, Chen Z, andLi H*(2017) YEATS domain - a histone acylation reader in health and disease.J Mol Biol, 429:1994-2002

6.Li Y, Zhao D, Chen Z, andLi H*(2017) YEATS domain: Linking histone crotonylation to gene regulation.Transcription, 8, 9-14

7.Noh K, Allis CD*, andLi H*(2016) Reading between the lines: “ADD”-ing histone and DNA methylation marks towards a new epigenetic “sum”.ACS Chem Biol11:554-563

8.Zhao S andLi H*(2015) Crystallography-based mechanistic insights into epigenetic regulation. Elsevier Publisher- Y. G. Zheng (ed.)Epigenetic Technological Applications:125-147

9.Li H*, Zhao S, and Patel DJ (2015) Histone recognition by tandem modules and modulation by multiple PTMs. Springer Books - Life Sciences and Biomedicine, M.-M. Zhou (ed.)Histone Recognition:149-172

10.Zhao S, Su X, Li Y, andLi H*(2015) Research advances in the mechanism of histone methylation recognition by reader modules.Science & Technology Review, 33(8): 94-100(in Chinese)

11.Wee S, Dhanak D,Li H, Armstrong SA, Copeland RA, Sims R, Goodman VL, Baylin SB, Liu XS, Tarakhovsky A, and Schweizer L*(2014) Targeting epigenetic regulators for cancer therapy.Ann NY Acad Sci1309:30-36

12.Li Y andLi H*(2012) Many keys to push: diversifying the ‘readership’ of plant homeodomain fingers.Acta Biochim Biophys Sin44 (1): 28-39

13.Li H#, Taverna SD#, Ruthenburg AJ#, Patel DJ, and Allis CD (2007) Readout of chromatin marks by histone-binding modules.Nat Rev Mol Cell Biol8(12) (#equal contribution) (Poster) (http://www.nature.com/nrm/posters/histonemarks/histonemarks.pdf)

14.Ruthenburg AJ,Li H, Patel DJ, and Allis CD (2007) Multivalent engagement of chromatin modifications by linked binding modules.Nat Rev Mol Cell Biol8(12):983-994

15.Taverna SD*#,Li H*#, Ruthenburg AJ, Allis CD, and Patel DJ* (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers.Nat Struct Mol Biol14(11):1025-1040 (#equal contribution & *correspondence)