李晴 :北京大学生命科学学院研究员

更新时间:2024-09-21 14:55

李晴,女,2001年获北京大学学士,2006年获博士学位。2006年至2011年在美国梅奥医学院癌症中心进行博士后研究。自2012年起,担任北京大学生命科学学院及北京大学-清华大学生命科学联合中心研究员。

人物经历

教育经历

2001 - 2006 , 理学博士 , 生物化学与分子生物学 , 北京大学

1997 - 2001 , 理学学士 , 生物化学与分子生物学 , 北京大学

工作经历

2019.02 - 今 教授 北京大学生命科学学院

2018.01 - 今 博雅特聘教授 北京大学生命科学学院

2018.02 - 2019.01 长聘副教授 北京大学生命科学学院

2012.01 - 2018.01 助理教授 北京大学生命科学学院

2012.01-今 研究员 北大清华生命科学联合中心

2006.09-2011.12 博士后 美国梅奥医学院癌症中心(Mayo Clinic Cancer Center)

主要成就

研究方向

1、脱氧核糖核酸复制偶联的核小体组装机制;  

2、表观遗传信息在子代细胞的分配机制;  

3、染色质复制维持基因组稳定性的机制。 

研究领域

主要研究染色质组装与表观遗传信息传递(Chromatin Assembly and Epigenetic Inheritance)机理。现代生命科学研究表明细胞中除了DNA以碱基排列所编码的基因组遗传信息,还有以核小体为基本结构单位组成的染色质所蕴含的表观遗传信息。细胞分裂过程中,随着基因组遗传信息的高保真复制,染色质结构蕴含的表观遗传信息也同样需要稳定传递,并且伴随基因组遗传信息被分配到子细胞中。染色质结构蕴含的表观遗传信息在子代细胞中的继承可能会主动或者被动变化,然而其机制尚不清楚,这也是生命科学领域最本质、最神秘的问题之一,和细胞的分化、增殖及多细胞生物的发育息息相关。研究表明,该过程的失调也与多种疾病相关,例如癌症、早衰和神经退行性疾病等。

研究的长期目标着眼于解决:1)染色质结构编码的表观遗传信息在细胞分裂的过程中是如何分配和传递的;2)该过程是如何参与维持基因组的稳定性;3)该过程失调如何导致人类疾病发生。

研究成果

2017年1月,李晴研究员研究组在DNA复制偶联的核小体组装的机制方面做出的重要突破发表《科学》 (Science,DOI: 10.1126/science.aah4712)上,该工作发现单链DNA结合蛋白RPA通过结合组蛋白H3-H4,形成一个高效的平台递呈组蛋白到新合成子链起始核小体组装。这一发现揭示一条全新的脱氧核糖核酸复制和核小体组装的偶联机制,大大促进染色质复制领域的发展。研究组首先发现RPA能够直接结合组蛋白H3-H4,结合在ssDNA的RPA可以促进H3-H4和相邻的dsDNA结合,这是核小体组装的起始步骤;用一系列体内体外方法,包括建立一个新的ReIN-Map方法,定量分析了酵母体内全基因组水平新合成DNA上核小体的分布,证明RPA在DNA复制偶联的核小体组装过程中重要作用。据此,提出在DNA复制偶联的核小体组装过程中,RPA-ssDNA配位化合物可以作为通用平台,方便多条分子伴侣呈递组蛋白通路连接到复制叉,从而促进子链DNA上核小体组装,揭示了一条新的将DNA复制和核小体组装相偶联的机制。

代表论文

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 脱氧核糖核酸 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, 多发性硬化症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 脱氧核糖核酸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 脱氧核糖核酸 replication. Cell \u0026 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 新陈代谢 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 \u0026 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., \u0026 Xu, D.Y. (2018) An OB-fold complex controls the repair pathways for 脱氧核糖核酸 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 脱氧核糖核酸 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 化学 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 脱氧核糖核酸 replication. Genes \u0026 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 脱氧核糖核酸 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

执教课程

分子生物学(本,主讲)

表观遗传学基础(本,主讲)

综合实验课(III)(本)

CLS生物化学与分子生物学模块(研)

现代生物学实验技术原理及其应用(研)

获得荣誉

2018 入选“北京高校卓越青年科学家”计划

2017 教育部青年科学奖

2017 国家杰出青年科学基金

2016 北京大学青年教师教学基本功比赛 理工科 二等奖

2015 郑昌学教学优秀奖

2014 拜耳集团学者奖

2013 国家优秀青年科学基金

2009 Mayo Clinic“肯达尔·詹娜Mayo 奖学金”

参考资料

北京大学生命科学学院导师教师师资介绍简介-李晴 - 北京大学考研导师.北京大学.2021-12-14

北京大学生命科学学院.北京大学生命科学学院.2021-12-08

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