李晴 教授
表观遗传学研究组
生命科学学院，北京大学-清华大学生命联合中心，北京大学
电话：
E-mail：li.qing@pku.edu.cn
1、染色质复制机制 (Chromatin Replication)
2、表观遗传信息传递机制 (Epigenetics Inheritance)
3、基因组稳定性维持机制 (Genome Stability Maintenance)
本实验室围绕解析染色质复制的机制，研究染色质复制在表观遗传信息传递中的作用，探讨表观遗传信息，基因组稳定性和细胞命运决定之间的关系。生命科学的核心问题之一是染色质结构所蕴含的表观遗传信息在细胞有丝分裂过程中传递到子细胞中。表观遗传信息传递的“启始”步骤发生在S期，伴随着整个基因组准确复制, 新合成的DNA的染色质高级结构必须重新建立来恢复细胞的整个表观遗传信息组。已有的研究结果表明DNA复制和染色质重建时相互偶联的，是生命个体正常发育的基础，因而对人类健康产生深远的影响。我们实验室一直在研究染色质复制和表观遗传信息传递的分子机制，目前主要工作是研究染色质的基本重复单位----核小体的组装是如何与DNA复制相偶联的，探讨此过程在基因组稳定性和异染色质建成的功能。
Li NN, Gao Y, Zhang YJ, Yu DQ, Lin JW, Feng JX, Li J, Xu ZC, Zhang YY, Dang SY, Zhou KD, Liu Y, Li XD, Tye BK, Li Q, Gao N, Zhai YL. (2024) Parental histone transfer caught at the replication fork. Nature, 627: 890-897.
Yu JT, Zhang YJ, Fang YM, Paulo JA, Yaghoubi D, Hua X, Shipkovenska G, Toda T, Zhang ZG, Gygi SP, Li Q, Moazed D. (2024) A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance. Cell, 187: 5010-5028.
Shi GJ, Yang CQ, Wu JL, Lei Y, Hu JZ, Feng JX, Li Q. (2024) DNA polymerase δ subunit Pol32 binds histone H3-H4 and couples nucleosome assembly with Okazaki fragment processing.Sci. Adv., 10: eado1739.
Zhao H, Li D, Xiao X, Liu GF, Su XY, Yan ZX, Gu SJ, Wang YZ, Li GH, Feng JX, Li W, Chen P, Yang JY, Li Q. (2024) Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin. iScience, 27: 108537.
Kang ZH, Li RM, Liu C, Dong XZ, Hu YX, Xu L, Liu XY, Xiang YF, Gao LM, Si WZ, Wang L, Li Q, Zhang L, Wang H, Yang XR, Liu J. (2024) m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells. Cell, 187: 6035-6054.
Liu YL, Zhangding ZR, Liu XH, Gan TT, Ai C, Wu JC , Liang HX , Chen MH, Guo YF, Lu RS, Jiang YP, Ji X, Gao N , Kong DC, Li Q, Hu JZ. (2024) Fork coupling directs DNA replication elongation and termination. Science, 383: 1215-1222.
Wang XZ, Tang YT, Xu JW, Leng H, Shi GJ, Hu ZF, Wu JL, Xiu YW, Feng JX, Li Q. (2023) The N-terminus of Spt16 anchors FACT to MCM2-7 for parental histone recycling. Nucl. Acids Res., 51: 11549-1567.
Du WL, Shi GJ, Shan CM, Li ZM, Zhu B, Jia ST, Li Q, Zhang ZG. (2022) Mechanisms of chromatin-based epigenetic inheritance. Sci. China-Life Sci., 65: 2162-2190.
Wang JC, Sang YC, Jin SX, Wang XZ, Azad GK, McCormick MA, Kennedy BK, Li Q, Wang JB, Zhang XN, Zhang Y, Huang YY. (2022) Single-cell RNA-seq reveals early heterogeneity during aging in yeast. Aging Cell., 21: e13712.
Leng H, Liu SF, Lei Y, Tang YT, Gu SJ, Hu JZ, Chen S, Feng JX, Li Q. (2021) FACT interacts with Set3 HDAC and fine-tunes GAL1 transcription in response to environmental stimulation. Nucleic Acids Res., 49: 5502- 5519.
Xu XL, Xu YX, Guo RY, Xu R, Fu CC, Xing MT, Sasanuma H, Li Q, Takata M, Takeda S, Guo R, Xu DY. (2021) Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress. Nat. Struct. Mol. Biol., 28: 487-500.
Liu Y, Ai C, Gan TT, Wu JC, Jiang YP, Liu XH, Lu RS, Gao N, Li Q, Ji X, Hu JZ. (2021) Transcription shapes DNA replication initiation to preserve genome integrity. Genome Biol.,22: 176.
Peng HY, Zhang SM, Peng YH, Zhu SY, Zhao X, Zhao XC, Yang SS, Liu GX, Dong Y, Gan XL, Li Q, Zhang XH, Pei HD, Chen XF. (2021)Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination.Adv. Sci., 8: e2100753.
Zhang YT, Ou XM, Wang XZ, Sun DJ, Zhou X Y, Wu XF, Li Q, Li L. (2021) Structure of the mitochondrial TIM22 complex from yeast. Cell Res., 31: 366-368.
Zhang WS, Feng JX, Li Q. (2020) The replisome guides nucleosome assembly during DNA replication. Cell Biosci., 10: 37.
Wan YCE, Leung TCS, Ding DB, Sun XL, Zhu L, Kang TZE, Yang D, Zhang YC, Qian CM, Huen MSY, Li Q, Chow MZY, Zheng ZL, Han JH, Goel A, Wang X, Ishibashi T, Chan KM. (2020) Cancer-associated histone mutation H2BG53D disrupts DNA-histone octamer interaction and promotes oncogenic phenotypes. Signal Transduct. Target. Ther., 5: 27.
冯建勋、严振鑫、张文硕、胡在峰、张煜婕、苏晓宇、吴佳乐、唐元桃、焦冠中、杨超淇、潘昊、陈雨、耿世辰、严湘奕、徐慧美
