Education
2001– 2006 Ph.D. Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China
1997– 2001 B.S. Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China
Professional Experience
2019.02 - Present Tenured Professor,School of Life Sciences, Peking University, Beijing, China
2018.02 - 2019.01 Tenured Associate Professor,School of Life Sciences, Peking University, Beijing, China
2012.01 - 2018.01 Assistant Professor, School of Life Sciences, Peking University, Beijing, China
2012.01 - Present Investigator, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
2011.04 –2011.12 Research Associate, Mayo Clinic College of Medicine, Rochester, MN, USA
2009.01 –2011.03 Senior Research Fellow, Mayo Clinic College of Medicine, Rochester, MN, USA
2006.09 –2008.12 Research Fellow, Mayo Clinic College of Medicine, Rochester, MN, USA
Social Services
2022-Present Member of Academic Degrees Committee of Biology, School of Life Sciences, Peking University
2019-Present Vice director of Undergraduate Training Committee in Biochemistry and Molecular Biology track, School of Life Sciences, Peking University
2018-Present Advisory Committee Member, National Talented High School Student Program, China Association for Science and Technology
2018-Present Member of Academic Committee, State Key Laboratory of Protein and Plant Gene Research
2018-Present Team leader of the Committee of PTN graduate program at Peking University
2012-2013 Member of Curriculum Design Committee of Center for Life Sciences
2012-2014 Member of the National Center for Protein Sciences- Protein Core Equipment Committee
Honors and Awards
2022 Mentoring Award, Peking University
2021 Undergraduate Teaching Excellence Award of Peking University
2018 Distinguished Young Scientist Award, Beijing Municipal Education Commission
2017 Young Scientist Award, Ministry of Education, China
2017 National Natural Science Funds for Distinguished Young Scholar
2017 Tang Lixin Scholarship
2016 Teaching Award, Peking University
2015 Zheng Changxue Teaching Award
2014 Bayer Investigator Award
2013 National Natural Science Funds for Outstanding Young Scholar
2009 Kendall-Mayo Fellowship
Grant Review/Study Section Membership
2022-Present Grant reviewer, Ministry of Science and Technology of China
2022-present Award reviewer, The Chinese Academy of Sciences
2019-Present Grant reviewer for Natural Science Founding, Beijing Municipal Education Commission, China
2014-Present Grant reviewer for Natural Science Founding of Life Sciences, National Natural Science Foundation of China
Teaching
Molecular Biology （Undergraduate course）
Epigenetics-From chromatin biology to human disease (Undergraduate course)
Biochemistry track module for CLS program
Chromatin Replication, Epigenetic Inheritance, & Genome Integrity
A key question in biology is how epigenetic states, defined by chromatin structure, are passed to daughter cells during mitosis. The first stage of epigenetic inheritance happens during the S phase of the cell cycle, when the entire genome is copied with high accuracy. At the same time, the chromatin structure must be carefully reconstructed on the new DNA to restore epigenetic information. The basic building block of chromatin is the nucleosome. Histone modifications within nucleosomes are the main carriers of epigenetic signals. Central to this process is the replication-related reconstruction of chromatin, especially the assembly of nucleosomes during DNA replication. Growing evidence suggests that these interconnected processes are vital to normal development and significantly affect human health.
We are particularly interested in elucidating the mechanisms governing chromatin replication. Our research aims to address two fundamental questions: first, to unravel how chromatin is faithfully duplicated during DNA synthesis, including the inheritance of epigenetic information and the principles underlying chromatin landscape reassembly; second, to understand how chromatin replication, in turn, regulates DNA replication to ensure genomic stability. By integrating these perspectives, we ultimately seek to decipher the mechanisms of cell fate determination under both physiological and pathological conditions, uncover the biological basis of development as well as diseases such as cancer and genetic disorders, and provide insights for diagnostic and therapeutic strategies.
Shi, G.J.＃, Yang, C.Q.＃, Wu, J.L.＃, Lei, Y., Hu, J.Z., Feng, J.X. *, & Li, Q. * (2024) DNA polymerase δ subunit Pol32 binds histone H3-H4 and couples nucleosome assembly with Okazaki fragment processing. Science Advances, 10(32): eado1739. 10.1126/sciadv.ado1739
Yu, J.T.＃, Zhang, Y.J.＃, Fang, Y.M., Paulo, J.A., Yaghoubi, D., Hua, X., Shipkovenska, G., Toda, T., Zhang, Z.G., Gygi, S. P., Jia, S.T., Li, Q.*, & Moazed, D.* (2024) A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance. Cell, 187(18): 5010–5028. e24. 10.1016/j.cell.2024.07.006
Li, N.N.＃, Gao, Y.＃, Zhang, Y.J.＃, Yu, D.Q.＃, Lin, J.W., Feng, J.X., Li, J., Xu, Z.C., Zhang, Y.Y., Dang, S.Y., Zhou, K.D., Liu, Y., Li, X. D., Tye, B. K.*, Li, Q.*, Gao, N.*, & Zhai, Y.L.* (2024) Parental histone transfer caught at the replication fork. Nature, 627(8005), 890–897, 10.1038/s41586-024-07152-2.
Zhao H.＃, Li D.＃, Xiao X.＃, Liu G.F., Su X.Y., Yan Z.X., Gu S.J., Wang Y.Z., Li G.H., Feng J.X., Li W., Chen P.*, Yang J.Y.*, Li Q.* (2024) Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin. iScience, 27(1), 108537, https://doi.org/10.1016/j.isci.2023.108537
Wang X.Z.＃, Tang Y.T.＃, Xu J., Leng H., Shi G.J., Hu Z.F., Wu J.L., Xiu Y.W., Feng J.X.*, Li Q.* (2023) The N-terminus of Spt16 anchors FACT to MCM2-7 for parental histone recycling. Nucleic Acids Research, 51:11549-11567, https://doi:10.1093/nar/gkad846
Leng, H.＃, Liu, S.F.＃, Lei, Y., Tang, Y.T., Gu, S.J., Hu, J.Z., Chen, S., Feng, J.X.*, 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
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. 2196 (117-141) Chapter 10, 978-1-0716-0867-8.
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), DOI: 10.15252/embj.201899154
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. DOI: 10.1007/s13238-017-0485-4.
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. doi: 10.1126/science.aah4712.
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(13), 1856-1867. doi: 10.1128/MCB.00152-16.
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(5), 1128-1141. doi: 10.1016/j.celrep.2015.12.096.
Dan Su#, Qi Hu#, Qing Li #, James R. Thompson, Gaofeng Cui, Ahmed Fazly, Brian A. Davies, Maria Victoria Botuyan, Zhiguo Zhang* & Georges Mer*.（2012）Structural basis for recognition of H3K56-acetylated histone H3–H4 by the chaperone Rtt106, Nature, ,483:104-107
Qing Li, Ahmed Fazly, Hui Zhou, Shengbing Huang, Zhiguo Zhang* and Bruce Stillman*. (2009) The Elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents. PLoS Genetics. 5 (10): e1000684.
Qing Li＃, Hui Zhou＃, Hugo Wurtele, Brian Davies, Bruce Horazdovasky, Alain Verreault* and Zhiguo Zhang*. (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.
Pei Han＃, Qing Li＃ and Yuxian Zhu*. (2008) Mutation of Arabidopsis BARD1 Causes Meristem Defects by Failing to Confine WUSCHEL Expression to the Organizing Center. The Plant Cell. 20: 1482-1493.
Research Progress
Chromatin replication involves a series of complex steps, including disassembling parental nucleosomes, unwinding double-stranded DNA (dsDNA), synthesizing daughter strands, and then assembling nucleosomes onto the newly formed DNA. This process occurs in a step-by-step manner and requires close coordination among all stages. At replication fork regions, two sources of histones contribute to nucleosome assembly: recycled parental histones from nucleosomes ahead of the fork and newly synthesized histones deposited onto the new DNA strands. These histones work together to fully protect the newly replicated DNA, creating a "busy histone traffic" at the fork. Two major protein complexes—the DNA replication machinery (the replisome) and the nucleosome assembly machinery (including histone chaperones and remodeling factors)—must communicate effectively to ensure that the process proceeds smoothly and in a highly coordinated manner. This dynamic interplay is essential not only for maintaining genome stability but also for ensuring faithful epigenetic inheritance.
Using budding yeast and mammalian cells as models, my laboratory has made significant contributions to chromatin replication and epigenetic inheritance.
1. Elucidate the molecular mechanisms underlying parental histone recycling at the fork front and its impact on epigenetic inheritance.
Parental histone recycling and transfer are vital for maintaining the epigenetic information encoded in histones. During DNA replication, parental nucleosomes with epigenetic marks are disrupted ahead of the replication forks to enable DNA unwinding and synthesis. To preserve the epigenetic landscape, these histones are recycled and transferred to the newly synthesized DNA strands. We found that FACT (FAcilitates Chromatin Transactions) associates with the replisome, facilitating the transfer of parental histones to both the leading and lagging strands. Additionally, we identified that the Fork Protection Complex (FPC), comprising Tof1, Csm3, and Mrc1, regulates histone recycling and distribution between daughter strands. A parental histone intermediate at the replication fork—a fully evicted histone hexamer [(H3-H4)₂-H2A-H2B]—was captured at the fork front.
a. Wang XZ#, Tang YT#, Xu JW, Leng H, Shi, GJ, Hu ZF, Wu JL, Xiu YW, Feng JX*, and Li Q*. The N-terminus of Spt16 anchors FACT to MCM2–7 for parental histone recycling, Nucleic Acids Research, 2023, 51(21): 11549-11567. PMID: 37850662
b. Li N#, Gao Y#, Zhang Yujie#, Yu D#, Lin J, Feng JX, Li J, Xu Z, Zhang Yingyi, Dang S, Zhou K, Liu Y, Li DX, Tye BK*, Li Q*, Gao N*, and Zhai Y*. Parental histone transfer caught at the replication fork, Nature, 2024, 627,890-897. PMID: 38448592
c. Yu JT#, Zhang YJ#, Fang YM, Paulo J, Yaghoubi D, Hua X, Shipkovenska G, Toda T, Zhang ZG, Gygi S, Jia ST, Li Q*, and Moazed D*. A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance. Cell 2024, 187,1-19. PMID: 39094570
2. Uncovering the coupling mechanism between nucleosome assembly and DNA replication
Over the last three decades, significant progress has been made (including ours) in understanding the functions of histone chaperones during the deposition of newly synthesized histone H3-H4 and the transfer of parental histones at the replication fork. However, how nucleosome assembly aligns with the replication machinery still needs to be clarified. We first discovered that the histone chaperone FACT interacts with CAF-1 and Rtt106 to facilitate the deposition of new histones at the replication fork. Additionally, we found that these histone chaperones interact with RPA, a protein complex that binds single-stranded DNA (ssDNA) at replication forks. RPA, best known for its roles in DNA replication and repair, binds directly to histone H3-H4 and promotes RC nucleosome assembly. We also observed that the Pol32 subunit of the Polδ complex binds directly to histone H3-H4 and aids in nucleosome assembly on the lagging strand. These findings present a new mechanism for coupling nucleosome assembly with DNA replication.
Additionally, we developed a new genome-wide analysis method (ReIN-Map) to monitor nucleosome occupancy patterns of nascent chromatin in cells. We also identified and characterized the first RPA chaperone, Rtt105, during chromatin replication, providing a new perspective on how ssDNA is assembled by RPA in different modes and how these assemblies influence signal initiation during DNA metabolism.
a. 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.
b. Liu, S.F.#, Xu, Z.Y. #, Leng, H. #, Zheng, P., Yang, J.Y., Chen, K.F., Feng, J.X., and Li, Q.* (2017). RPA binds histone H3-H4 and functions in DNA replication-coupled nucleosome assembly. Science 355, 415-420.
c. Shi GJ#, Yang CQ#, Wu JL#, Lei Y, Hu JZ, Feng JX*. and Li Q*. DNA polymerase δ subunit Pol32 binds histone H3-H4 and couples nucleosome assembly with Okazaki fragment processing. Science Advances, 2024 DOI: 10.1126/sciadv.ado1739
d. Xu, Z.Y., Feng, J.X.* and Li, Q.* (2021) Measuring Genome-Wide Nascent Nucleosome Assembly Using Replication-intermediate nucleosome mapping (ReIN-Map) In Yeast Protocols, Methods Molecular Biology (Book) 2196, (ed. Xiao, W.) 117-141. Humana Press, New York, NY. https://doi.org/10.1007/978-1-0716-0868-5_10.
e. 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.
3. Understand the role of chromatin replication factors in cell fate determination
Chromatin dynamics are crucial for normal development, as chromatin states must be reconfigured during differentiation and maintained during proliferation. Recent research shows that factors involved in replication-coupled (RC) nucleosome assembly, especially histone chaperones, play a key role in preserving gene expression patterns across successive cell divisions. FACT, a highly conserved histone chaperone, is essential for proliferating cells. Abnormal expression or mutations in FACT are linked to cancer and neurodegenerative diseases, directly impacting cell fate decisions. However, understanding the precise mechanisms of FACT is challenging since its disruption can cause widespread changes in various DNA processes. To explore this, we used separation-of-function mutant alleles (spt16-G132D, spt16-DN, and SSRP1-Q265K) to pinpoint FACT's specific roles in different biological contexts.
Our results demonstrate how modifying the activity of histone chaperones on chromatin can significantly impact nucleosome arrangement. This, in turn, affects transcriptional regulation, emphasizing the crucial role of precise gene expression control in guiding cell fate decisions during early development and enabling quick, cost-effective responses to environmental changes.
a. Zhao H#, Li D#, Xiao X#, Liu CF, Chen GF, Su XY, Yan ZX, Gu SJ, Wang YZ, Li, GH, Feng JX, Li W, Chen P*, Yang JY*, and Li Q*. Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin, iScience, 2024, 27(1): 108537.
b. Leng, H.＃, Liu, S.F.＃, Lei, Y., Tang, Y.T., Gu, S.J., 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 49, 5502-5519.
c. 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.
d. 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.
