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李海涛


李海涛

 

电子邮件:lht@tsinghua.edu.cn

电话: +86-10-62771392 (办公室)



研究方向:

  本实验室研究方向是表观遗传调控的分子结构基础。表观遗传调控关注染色质层面遗传信息的组织与解读,具体机制涉及到组蛋白或DNA/RNA修饰、组蛋白变体、染色质重塑以及非编码RNA等。表观遗传机制在从基因表达调控到细胞命运决定的等众多生命过程中发挥着关键作用。与此同时,越来越多证据揭示表观遗传调控异常会导致各种人类疾病的发生,尤其是癌症。我们主要通过结构生物学手段,并结合其它生物化学、化学生物学、细胞生物学技术,研究表观遗传调控过程中的分子识别与催化事件。此外,我们也在积极开展基于结构的表观调控因子分子改造和基于结构的表观药物发现研究。


代表性科研论文(*通讯作者)


研究论文

1. 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 Biol (accepted)

2. 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. Nature 543, 265-269 ( #co-senior author)

3. Xiong X, Panchenko T, Yang S, Zhao S, Yan P, Zhang W, Xie W, Li Y, Zhao Y, Allis CD, and Li H* (2016) Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2. Nat Chem Biol 12:1111-1118

4. Yang S, Zheng X, Lu C, Li G-M, Allis CD, and Li H* (2016) Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase. Genes Dev 30:1611-1616

5. 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 Cell 63:470-484 

6. 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 Commun 7:11874

7. Zhang X, Zhao D, Xiong X, He Z, and Li H* (2016) Multifaceted histone H3 methylation and phosphorylation readout by the plant homeodomain (PHD) finger of human nuclear antigen Sp100C. J Biol Chem 291:12786-12798

8. Zhao D, Guan H, Zhao S, Mi W, Wen H, Li Y, Zhao Y, Allis CD, Shi X*, and Li H* (2016) YEATS2 is a selective histone crotonylation reader. Cell Research 26:629–632

9. Li Y, Sabari BR, Panchenko T, Wen H, Zhao D, Guan H, Wan L, Tang Z, Zhao Y, Roeder R. Shi X, Allis CD*, and Li H* (2016) Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain. Mol Cell 62:181-193

10. Zhao D, Zhang X, Guan H, Xiong X, Shi Xi, Deng H, and Li H* (2016) The BAH domain of BAHD1 is a histone H3K27me3 reader. Protein Cell  7: 222-226 

11. Wu R, Yue Y, Zheng X, and Li H* (2015) Molecular basis for histone N-terminal methylation by NRMT1. Genes Dev 29:2337-2342

12. 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 Commun 6: 8911

13. 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 Cell 59:89-103

14. 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 USA 112(22): 6820-6827

15. 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. Cell 159:558-571

16. 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. Nature 507, 263-268

17. Su X, Zhu G, Ding X, Lee SY, Dou Y, Zhu B, Wu W*, and Li H* (2014) Molecular basis underlying histone H3 lysine-arginine methylation patter readout by Spin/Ssty repeats of Spindlin1. Genes Dev 28:622-636

18. 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 USA 111: E345-E363 

19. 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 Biol 18: 769-776 

20. 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. Cell 145: 692-706

21. 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. Nature 457, 57-62

22. 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 Cell 34(2), 155-167 (#equal contribution)

23. 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 Cell 28, 677-691

24. 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. Nature 442, 91-95

 

综述与图书章节(*通讯作者)

1. Zhao D, Li Y, Xiong X, Chen Z, and Li H* (2017) YEATS domain - a histone acylation reader in health and disease. J Mol Biol, http://dx.doi.org/10.1016/j.jmb.2017.03.010

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

3. Noh K, Allis CD*, and Li H* (2016) Reading between the lines: “ADD”-ing histone and DNA methylation marks towards a new epigenetic “sum”. ACS Chem Biol 11:554-563

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

5. 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 

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

7. 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 Sci 1309:30-36

8. Li Y and Li H* (2012) Many keys to push: diversifying the ‘readership’ of plant homeodomain fingers. Acta Biochim Biophys Sin 44 (1): 28-39

9. Li H#, Taverna SD#, Ruthenburg AJ#, Patel DJ, and Allis CD (2007) Readout of chromatin marks by histone-binding modules. Nat Rev Mol Cell Biol 8(12)  (#equal contribution) (http://www.nature.com/nrm/posters/

histonemarks/histonemarks.pdf) 

10. Ruthenburg AJ, Li H, Patel DJ, and Allis CD (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 8(12):983-994

11. 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 Biol 14(11):1025-1040  (#equal contribution)

 
 

 

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