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李晴

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李晴

电子邮件: Li.qing(at)pku(dot)edu(dot)cn;

电话: +86-10-62752516;

实验室主页:?http://bio.pku.edu.cn/teacher_dis_oa.php?cid=146&&teaid=36

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研究方向染色质复制与表观遗传信息传递 (Chromatin Replication & Epigenetic Inheritance)

生命科学领域的一个核心问题是多细胞生物如何将同一个基因组展示成众多形态与功能迥异的不同类型细胞的转录组,例如人体中高度分工的数百种细胞。染色质既是编码的基因组信息的DNA的保护神,又是其信息解调器。表观遗传学就是在染色质层面研究基因组信息的复制和解调,探索染色质在生殖发育、细胞编程与重编程、衰老与疾病发生等过程的作用。

本实验室致力于探索染色质复制与表观遗传信息传递的分子机制,探讨表观遗传信息在基因组稳定性和细胞命运决定中的作用。作为染色质的基本结构单位,核小体在辅助因子的作用下层层折叠,组装成高度有序的染色质,有效的压缩和保护DNA而且蕴藏丰富的表观遗传信息,在时空间上精细调节基因组的信息有序输出和复制,确保生命个体的正常发育并对外界刺激做出应答。表观遗传信息的传递包括了细胞分裂周期中染色质的复制和表观遗传信息在子代间的分配。DNA复制时复制叉前的“父本”核小体先解组装,然后回收的“父本”和新合成”的组蛋白在新生DNA子链上重新组装成核小体,这个过程被称为DNA复制偶联的核小体组装。而且细胞分裂通过某种机制将两条姐妹染色体及其携带的表观遗传信息被分配到两个子细胞中,子细胞继承的表观遗传信息的改变与细胞的命运决定密切相关。DNA复制偶联核小体组装不仅受组蛋白分子伴侣和修饰调控,同时和DNA复制元件密切相关,是理解表观遗传信息在细胞分裂过程中继承机制的核心步骤。数据表明,该过程的失调与多种疾病相关,包括肿瘤、神经退行性病变和早衰等,揭示染色质复制机制有助于解析人类疾病发生和发展的分子机理,为肿瘤诊疗、器官修复及药物设计等提供理论指导。

本实验室以酵母和哺乳动物细胞为模式,从DNA复制偶联的核小体组装入手,研究染色质复制和表观遗传信息传递的分子机制,揭示染色质复制在基因组稳定性维持及细胞命运决定等方面的功能。研究方向主要包括:

1DNA复制偶联的核小体组装机制;

2、染色质复制、高级结构重建及其维持基因组稳定性的机制;

3、表观遗传信息的分配和细胞命运决定中的机制。?

代表性科研论文:(# 共同第一作者, *通讯作者)

Research Articles

1.???????? Li, S.Q#., Dong, Z.Q#., Yang, S.S., Feng, J.X. and Li, Q* (2019) Chaperoning RPA during DNA metabolism. Current Genetics doi: 10.1007/s00294-019-00945-3. Review

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

3.???????? 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.

4.???????? 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.

5.???????? 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.

6.???????? Li, W., Chen, P., Yu, J., Dong, 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.

7.???????? Feng, J.X., Gan, H.Y., Eaton, M.L., Zhou, H., Li, S.Q., Belsky, J.A., MacAlpine, D.M., 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.

8.???????? Yang, J.Y., Zhang, X., Feng, J.X., Leng, H., Li, S.Q., Xiao, J.X., Liu, S.F., Xu, Z.Y., Xu, J.W., Li, D., Wang, Z.S., Wang, J.Y., and Li, Q.* (2016). The histone chaperone FACT contributes to DNA replication-coupled nucleosome assembly. Cell Reports 14, 1128-1141.

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

10.???? Li, Q., Burgess, R., and Zhang, Z.G.* (2012). All roads lead to chromatin: Multiple pathways for histone deposition. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1819, 238-46.

11.???? Li, Q., and Zhang, Z.G.* (2012). Linking DNA replication to heterochromatin silencing and epigenetic inheritance. Acta Biochimica et Biophysica Sinica (ABBS) 44, 3-13.

12.???? 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.

13.???? 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 DNA damage agents. PLoS Genetics 5, e1000684.

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

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