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李晴
來源:互聯網

李晴,女,2001年獲北京大學學士,2006年獲博士學位。2006年至2011年在美國梅奧醫學院癌癥中心進行博士后研究。自2012年起,擔任北京大學生命科學學院及北京大學-清華大學生命科學聯合中心研究員。

人物經歷

教育經歷

2001 - 2006 , 理學博士 , 生物化學與分子生物學 , 北京大學

1997 - 2001 , 理學學士 , 生物化學與分子生物學 , 北京大學

工作經歷

2019.02 - 今 教授 北京大學生命科學學院

2018.01 - 今 博雅特聘教授 北京大學生命科學學院

2018.02 - 2019.01 長聘副教授 北京大學生命科學學院

2012.01 - 2018.01 助理教授 北京大學生命科學學院

2012.01-今 研究員 北大清華生命科學聯合中心

2006.09-2011.12 博士后 美國梅奧醫學院癌癥中心(Mayo Clinic Cancer Center)

主要成就

研究方向

1、脫氧核糖核酸復制偶聯的核小體組裝機制;  

2、表觀遺傳信息在子代細胞的分配機制;  

3、染色質復制維持基因組穩定性的機制。 

研究領域

主要研究染色質組裝與表觀遺傳信息傳遞(Chromatin Assembly and Epigenetic Inheritance)機理。現代生命科學研究表明細胞中除了DNA以堿基排列所編碼的基因組遺傳信息,還有以核小體為基本結構單位組成的染色質所蘊含的表觀遺傳信息。細胞分裂過程中,隨著基因組遺傳信息的高保真復制,染色質結構蘊含的表觀遺傳信息也同樣需要穩定傳遞,并且伴隨基因組遺傳信息被分配到子細胞中。染色質結構蘊含的表觀遺傳信息在子代細胞中的繼承可能會主動或者被動變化,然而其機制尚不清楚,這也是生命科學領域最本質、最神秘的問題之一,和細胞的分化、增殖及多細胞生物的發育息息相關。研究表明,該過程的失調也與多種疾病相關,例如癌癥、早衰和神經退行性疾病等。

研究的長期目標著眼于解決:1)染色質結構編碼的表觀遺傳信息在細胞分裂的過程中是如何分配和傳遞的;2)該過程是如何參與維持基因組的穩定性;3)該過程失調如何導致人類疾病發生。

研究成果

2017年1月,李晴研究員研究組在DNA復制偶聯的核小體組裝的機制方面做出的重要突破發表《科學》 (Science,DOI: 10.1126/science.aah4712)上,該工作發現單鏈DNA結合蛋白RPA通過結合組蛋白H3-H4,形成一個高效的平臺遞呈組蛋白到新合成子鏈起始核小體組裝。這一發現揭示一條全新的脫氧核糖核酸復制和核小體組裝的偶聯機制,大大促進染色質復制領域的發展。研究組首先發現RPA能夠直接結合組蛋白H3-H4,結合在ssDNA的RPA可以促進H3-H4和相鄰的dsDNA結合,這是核小體組裝的起始步驟;用一系列體內體外方法,包括建立一個新的ReIN-Map方法,定量分析了酵母體內全基因組水平新合成DNA上核小體的分布,證明RPA在DNA復制偶聯的核小體組裝過程中重要作用。據此,提出在DNA復制偶聯的核小體組裝過程中,RPA-ssDNA配位化合物可以作為通用平臺,方便多條分子伴侶呈遞組蛋白通路連接到復制叉,從而促進子鏈DNA上核小體組裝,揭示了一條新的將DNA復制和核小體組裝相偶聯的機制。

代表論文

Jianxun Feng#, Haiyun Gan#, Matthew L. Eaton, Hui Zhou, Shuqi Li, Jason A. Belsky, David M. MacAlpine, Zhiguo Zhang* and Qing Li*, Non-codingtranscription is a driving force for nucleosome instability in spt16 mutant cells,Molecular and Cellular Biology, 2016, 36:1856-1867. (Article of significant interest Selected as Spotlight)

Jiayi Yang#, Xu Zhang#, Jianxun Feng#, He Leng, Shuqi Li, Junyu Xiao, Shaofeng Liu, Zhiyun Xu, Jiawei Xu, Di Li, Zhongshi Wang, Jingyang Wang, Qing Li*, The histone chaperone FACT contributes to 脫氧核糖核酸 replication-coupled nucleosome assembly,Cell Reports, 2016,14: 1128-1141.

Qing Li#, Rebecca Burgess#, and Zhiguo Zhang* , All roads lead to chromatin: Multiple pathways for histone deposition,Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2012, 1819: 238-46, Review.

Leng, H.#, Liu, S.F.#, Lei, Y., Tang, Y.T., Gu, Super Junior, Hu, J.Z., Chen, S., Feng, J.X.* and Li, Q*. (2021) FACT interacts with Set3 HDAC and fine-tunes GAL1 transcription in response to environmental stimulation. Nucleic Acids Research, gkab312, https://doi.org/10.1093/nar/gkab312

Tian, T.#, Bu, M.#, Chen, X.#, Ding, L.L.#, Yang, Y.L.#, Han, J.H., Feng, X.H., Xu, P.L., Liu, T., Ying, S.M., Lei, Y., Li, Q., and Huang, J.*, (2021) The ZATT-TOP2A-PICH axis drives extensive replication fork reversal to promote genome stability. Molecular Cell 81: 198-211.e6.

Kang, T.Z.E#., Zhu, L.#, Yang, D., Ding, D., Zhu, X., Wan, Y.C.E., Liu, J., Ramakrishnan, S., Chan,L., Chan, SY., Wang, X., Gan, HY., Han, JH., Ishibashi, T., Li, Q. and Chan, K.M.*. (2021) The elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer. J Biol Chem,296:100374. doi: 10.1016/j.jbc.2021.100374.

Zhang, Y.T.#, Ou, X.M.#, Wang, X.Z. , Sun, D.J., Zhou, X.Y., Wu, X.F., Li, Q. , Li, L.*, (2020)Structure of the mitochondrial TIM22 complex from yeast. Cell Research, https://doi.org/10.1038/s41422-020-00399-0.

Wan, Y.C.E.#, Leung, T.C.S.#, Ding, D.B.#, Sun, X.L., Zhu, L., Kang, T.Z.E., Yang, D., Zhang, Y.C., Qian, C.M., Huen, 多發性硬化癥Y., Li, Q., Chow, M.Z.Y., Zheng, Z.L., Han, J.H., Goel, A., Wang, X.*, Ishibashi, T.*, Chan, K.M.*. (2020) Cancer-associated histone mutation H2BG53D disrupts 脫氧核糖核酸histone octamer interaction and promotes oncogenic phenotypes. Signal Transduction and Targeted Therapy, 5(1):27 https://doi.org/10.1038/s41392-020-0131-0.

Xu, Z.Y., Feng, J.X*. and Li, Q* . (2020) Measuring Genome-Wide Nascent Nucleosome Assembly Using Replication-intermediate nucleosome mapping (ReIN-Map). Methods Molecular Biology (Book) Vol.2196. Chapter 10, 978-1-0716-0867-8.

Zhang, W.S.., Feng J.X.*, and Li, Q.* (2020) The rePL/Isome guides nucleosome assembly during 脫氧核糖核酸 replication. Cell & bioscience. 10.1186/s13578-020-00398-z.

Li, S.Q#., 越南盾, Z.Q#., Yang, S.S., Feng, J.X., and Li, Q*. (2019) Chaperoning RPA during DNA 新陳代謝 Current Genetics  doi: 10.1007/s00294-019-00945-3

Li, Q*., Zhang, X., and Zhang, Z.* (2018). CHAF1B overexpression: A brake for the differentiation of 白血病 cells. Cancer Cell 34:693-694.

Li, S.Q#, Xu, Z.Y. #, Xu, J.W. #, Zuo, L.Y., Yu, C.H., Zheng, P., Gan, H.Y., Wang, X.Z., Li, L.T., Sharma, S., Chabes, A., Li, D., Wang, S., Zheng, S.H., Li, J.B., Chen, X.F., Sun, Y.J., Xu, D.Y., Han, J.H., Chan, K.M., Qi, Z., Feng, J.X.*, and Li, Q.* (2018) Rtt105 functions as a chaperone for replication protein A to preserve genome stability The EMBO Journal e99154.(Article recommended by F1000)

Yan, X.W#., Yang, J.Y#., Xu, J.W#., Feng, J.X*., and Li, Q.* (2018). Histone chaperone Spt16p is required for heterochromatin mediated silencing in budding yeast. Protein & Cell 9:652-658.

Gao, S.X., Feng, S.M., Ning, S.K., Liu, J.Y., Zhao, H.Y., Xu, Y.X., Shang, J.F., Li, K.J., Li, Q., Guo, R., & Xu, D.Y. (2018) An OB-fold complex controls the repair pathways for 脫氧核糖核酸 double-strand breaks. Nature Communications 9: 3925.

Liu, S.F.#, Xu, Z.Y. #, Leng, H. #, Zheng, P., Yang, J.Y., Chen, K.F., Feng, J.X., Li, Q. * (2017). RPA binds histone H3-H4 and functions in DNA replication-coupled nucleosome assembly. Science 355, 415-420.

Li, W.#, Chen, P.#, Yu, J., 越南盾, L.P., Liang, D., Feng, J.X., Yan, J., Wang, P.Y., Li, Q., Zhang, Z.G., Li, M.*, and Li, G.H.* (2016). FACT remodels the tetranucleosomal unit of chromatin fibers for gene transcription. Molecular Cell 64, 120-133.

Feng, J.X.#, Gan, H.Y.#, Eaton, M.L., Zhou, H., Li, S.Q., Belsky, J.A., MacAlpine, 糖尿病, Zhang, Z.G.* and Li, Q.* (2016). Noncoding transcription is a driving force for nucleosome instability in spt16 mutant cells. Molecular and Cellular Biology 36, 1856-1867. Article of significant interest selected as a Spotlight.

Zhang, X., and Li, Q.* (2014). A role of histone modifications during chromatin replication. Chinese Bulletin of Life Sciences 26, 1176-1186. (In Chinese)

Su, D.#, Hu, Q.#, Li, Q.#, Thompson, J.R., Cui, G.F., Fazly, A., Davies, B.A., Botuyan, M.V., Zhang, Z.G.* and Mer, G.* (2012). Structural basis for recognition of H3K56-acetylated histone H3–H4 by the chaperone Rtt106. Nature 483, 104-107 (# Co-first author).

Li, Q., and Zhang, Z.G.* (2012). Linking 脫氧核糖核酸 replication to heterochromatin silencing and epigenetic inheritance. Acta Biochimica et Biophysica Sinica (ABBS) 44, 3-13. This review was selected as the cover story.

Fazly, A., Li, Q., Hu, Q., Mer, G., Horazdovsky, B. and Zhang, Z.G.* (2012). Histone chaperone Rtt106 promotes nucleosome formation using (H3-H4)2 tetramers. The Journal of Biological 化學 2287, 10753-10760.

Burgess, R., Zhou, H., Han, J.H., Li, Q., and Zhang, Z.G.* (2012). The SCFDia2 ubiquitin E3 ligase ubiquitylates Sir4 and functions in transcriptional silencing.  PLoS Genetics  8, e1002846

Han, J.H., Li, Q., McCullough, L., Formosa, T. and Zhang, Z.G.* (2010). Ubiquitylation of FACT by the Cullin-E3 ligase Rtt101 connects FACT to 脫氧核糖核酸 replication. Genes & Development 24, 1485-1490.

Li, Q., Fazly, A., Zhou, H., Huang, H.S., Zhang, Z.G.* and Stillman, B.* (2009). The Elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to 脫氧核糖核酸 damage agents. PLoS Genetics 5, e1000684.

Li, Q.#, Zhou, H.#, Wurtele, H., Davies, B., Horazdovasky, B., Verreault, A.* and Zhang, Z.G.* (2008). Acetylation of Histone H3 lysine 56 regulates CAF-1 dependent nucleosome assembly. Cell 134,244-255 (# Co-first author). Previewed in the same issue. Highlighted in Nature Reviews Molecular Cell Biology, September 2008

執教課程

分子生物學(本,主講)

表觀遺傳學基礎(本,主講)

綜合實驗課(III)(本)

CLS生物化學與分子生物學模塊(研)

現代生物學實驗技術原理及其應用(研)

獲得榮譽

2018 入選“北京高校卓越青年科學家”計劃

2017 教育部青年科學獎

2017 國家杰出青年科學基金

2016 北京大學青年教師教學基本功比賽 理工科 二等獎

2015 鄭昌學教學優秀獎

2014 拜耳集團學者獎

2013 國家優秀青年科學基金

2009 Mayo Clinic“肯達爾·詹娜Mayo 獎學金”

參考資料 >

北京大學生命科學學院導師教師師資介紹簡介-李晴 - 北京大學考研導師.北京大學.2021-12-14

北京大學生命科學學院.北京大學生命科學學院.2021-12-08

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