林承棋教授，博士生导师
个人简介：
林承棋，二级教授，首席教授，博士生导师，国家级青年人才，国家重点研发计划项目首席科学家，“万人计划”中青年科技创新领军人才。主要研究方向：1、基因表达调控机制；2、细胞命运决定与早期胚胎发育调控。在Cell、Nature Cell Biology、Molecular Cell、Cell Death and Differentiation、Genes & Development、Science Advances等杂志发表SCI论文30 余篇，引用4000余篇次。现主持国家重点研发项目、基金委重点项目及面上项目。曾获新加坡国家医学研究理事会(NMRC)转化与临床研究、新加坡卫生部物医药研究理事会(BMRC)项目、江苏省杰出青年基金，江苏省“双创人才“等多项基金资助。
教育和工作简历：
1998至2003年，东南大学，临床医学，学士
2003至2006年，东南大学，遗传学，硕士
2006至2008年，新加坡国立大学，研究助理
2008至2013年，美国Stowers Institute for Medical Research，分子与细胞生物学，博士
2013至2016年，新加坡Institute of Molecular and Cell Biology，A-STAR，Young Investigator
2016至今，东南大学，生命科学与技术学院，教授
研究方向：
1.【基因表达调控机制】
基因表达调控是细胞生命活动的基础。基因差异性表达在细胞命运决定、个体发育以及疾病的发生发展中起到决定性作用。RNA 聚合酶 II（Pol II）启动子近端暂停是一种进化上保守、从细菌到人类普遍存在的基因表达调控机制；其在早期胚胎发育、免疫反应、应激反应等生命过程中发挥重要作用。实验室在国际上首次鉴定了超级转录延伸复合物Super Elongation Complex (SEC) SEC 可通过磷酸化 Pol II， SPT5 及 NELF，促进 Pol II 从暂停状态进入有效转录延伸阶段，进而调控机体应激及发育相关基因的快速协调性转录激活。（Molecular Cell, 2010；Genes&Development, 2011；Cell, 2013）。近期的研究发现，SEC介导的多价相分离在RNA聚合酶II转录暂停释放中起着关键作用，并从全新的角度为基因快速协调性转录激活程序的机制探索提供了新的认识（Science Advance,2020；EMBO reports,2023）。实验室将继续致力于基因转录调控的新机制探究，及其失调如何驱动疾病发生发展。
增强子可以跨越远距离基因组序列，精准的在时间和空间上控制基因表达。因此，增强子精准匹配靶标启动子，是基因调控网络研究的重中之重。近年来，增强子表观遗传学研究表明在胚胎发育早期阶段存在多种不同状态的增强子来维持其多向分化潜能。目前对于处于暂停或失活状态的增强子的功能尚不清楚。课题组在国际上首次报道转录延伸因子ELL3可结合在暂停状态的启动子上，调控RNA Pol II暂停，进而调控增强子的活性及干细胞多能性（Cell，2013）；近期的研究，进一步发现ELL3结合的L1NE-1 5’UTR可作为一类全新的增强子元件，调控早期胚胎发育，其功能异常将会导致胚胎发育缺陷、流产（Nat Cell Biol, 2023，封面文章）。我们将进一步探究增强子-启动中互作的特异性，及其介导的基因表达特异性在干细胞多向分化潜能和早期胚胎发育中的作用和分子机理。
2.【细胞命运决定与早期胚胎发育调控】
细胞命运决定贯穿发育和疾病全过程，其核心是基因差异性表达。合子基因组激活(human zygotic genome activation, ZGA)作为启动胚胎发育进程的关键事件，标志着受精后基因表达的起始，这一过程取决于RNA聚合酶II对合子基因组启动子的有序识别，同时也受到染色质的结构和转录因子的协同调控。我们将进一步探究合子基因组激活的转录及表观遗传调控机理；其次，明确ZGA对胚胎全能性、多能性及胚层发育的影响及调控机制；同时探究早期胚胎发育过程中转座元件的意外作用。本研究将丰富人们对早期胚胎发育、合子基因组激活等方面的生物学机制的认识；对辅助生殖、优生优育等的基础生物学研究和临床诊疗也具有重要的指导价值。
心脏是第一个形成的器官。其形成与再生异常，可分别导致先天性心脏病和成人心脏病。先天性心脏病是我国最常见的出生缺陷，约占28%，是影响我国新生人口健康的重大公共卫生问题。大量研究显示，胚胎时期心脏发育异常是导致先天性心脏缺陷的主要原因。在早期心脏发育过程中，心脏前体细胞的动态演化路径是什么？心脏细胞存在哪些不同的分化来源？不同来源的心脏前体细胞受到哪些关键的转录因子与基因组调控元件的影响？这些问题的解答对于我们理解心脏早期发育过程，进而治疗心脏发育疾病至关重要。
代表性论文：（†通讯作者）
1. Xie P*, Zhu S*, Zhang J*, Wang X, Jiang X, Xiong F, Chen L, Fang K, Ji Y, Zheng B, Da L, Cao H, Sun Y†, Luo Z†, Lin C†. 4D live tracing reveals distinct movement trajectories of meiotic chromosomes. Life medicine, 2024 Aug (Accepted).
2. Xie P*, Jiang X*, He J*, Pan Q*, Yang X*, Zheng Y*, Fan W, Wu C, Zheng W, Fang K, Si S, Zhu S, Yang Y, Zhong T, Yang Z, Wei K, Xie W, Jing N†,Luo Z†, Lin C†.Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics. Elife. 2024 Jul:98293v1.
3. Mao G*, Yang Y*, Luo Z†, Lin C†，Xie P†. SpatialQC: transcriptome data automated quality control for spatial transcriptome data. Bioinformatics, 2024 Aug 2;40(8):btae458.
3. Meng S*, Liu X*, Zhu S*, Xie P*, Fang H, Pan Q, Fang K, Li F, Zhang J, Che Z, Zhang Q, Mao G, Wang Y, Hu P, Chen K, Sun F, Xie W, Luo Z†, Lin C†. Young LINE-1 transposon 5’UTRs marked by elongation factor ELL3 function as enhancers to regulate naïve pluripotency in embryonic stem cells. Nat Cell Biol. 2023 Aug 17. （封面文章）
4. Che Z*, Liu X*, Dai Q*, Fang K, Guo C, Yue J, Fang H, Xie P, Luo Z†, Lin C†. Distinct roles of the two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA Pol II transcription elongation. J Mol Cell Biol. 2023 Aug 1:mjad049.
5. Guo C, Zhang Y, Shuai S, Sigbessia A, Hao S, Xie P, Jiang X, Luo Z†, Lin C†. The super elongation complex (SEC) mediates phase transition of SPT5 during transcriptional pause release. EMBO Rep. 2023 Jan 11:e55699. （同期杂志述评）
6. Guo C, Luo Z†, Lin C†. Phase Separation Properties in Transcriptional Organization. Biochemistry. 2022 Nov 15;61(22):2456-2460.
7. Zhao X*, Fang K*, Liu X, Yao R, Wang M, Li F, Hao S, He J, Wang Y, Fan M, Huang W, Li Y, Gao C, Lin C†, Luo Z†. QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis. Cell Death Differ. 2022 Nov 12.
8. Wang Y, Ma B, Liu X, Gao G, Che Z, Fan M, Meng S, Zhao X, Sugimura R, Cao H, Zhou Z, Xie J, Lin C†, Luo Z†. ZFP281-BRCA2 prevents R-loop accumulation during DNA replication. Nat Commun. 2022 Jun 17;13(1):3493.
9. Guo C, Luo Z, Lin C. Phase separation, transcriptional elongation control, and human diseases. J Mol Cell Biol. 2021 Aug 4;13(4):314-318. （封面文章）
10. Yue J, Dai Q, Hao S, Zhu S, Liu X, Tang Z, Li M, Fang H, Lin C, Luo Z. Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells. J Biol Chem. 2021 Jan-Jun;296:100319.
11. Du H*, Chen C*, Wang Y, Yang Y, Che Z, Liu X, Meng S, Guo C, Xu M, Fang H, Wang F, Lin C†, Luo Z†. RNF219 interacts with CCR4-NOT in regulating stem cell differentiation. J Mol Cell Biol. 2020 Oct 26;12(11):894-905.
12. Han Z, Cui K, Placek K, Hong N, Lin C, Chen W, Zhao K, Jin W. Diploid genome architecture revealed by multi-omic data of hybrid mice. Genome Res. 2020 Aug; 30(8):1097-1106.
13. Guo C, Che Z, Yue J, Xie P, Hao S, Xie W, Luo Z†, Lin C†. ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation. Sci Adv. 2020 Apr 1;6(14):eaay4858.
14. Luo Z, Liu X, Xie H, Wang Y, Lin C †. ZFP281 recruits MYC to active promoters in regulating transcriptional initiation and elongation. Mol Cell Biol. 2019 Sep 30. pii: MCB.00329-19.
15. Zhang Y, Wang C, Liu X, Yang Q, Ji H, Yang M, Xu M, Zhou Y, Xie W, Luo Z, Lin C †. AFF3-DNA methylation interplay in maintaining the mono-allelic expression pattern of XIST in terminally differentiated cells. J Mol Cell Biol. 2018 Dec 7. （同期杂志述评）
16. Wu J, Tao N, Tian Y, Xing G, Lv H, Han J, Lin C, Xie W. Proteolytic maturation of Drosophila Neuroligin 3 by tumor necrosis factor α-converting enzyme in the nervous system. Biochim Biophys Acta. 2017 Oct 28. Pii: S0304-4165(17)30350-1.
17. Dai Q*, Shen Y*, Wang Y*, Wang X, Francisco JC, Luo Z, Lin C †. Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells. Nucleic Acids Res. 2017 Sep 25.
18. Francisco JC, Dai Q, Luo Z, Wang Y, Chong RH, Tan YJ, Xie W, Lee GH, Lin C †. Transcriptional elongation control of the HBV cccDNA transcription by Super Elongation Complex (SEC) and BRD4. Mol Cell Biol. 2017 Jul 10. pii: MCB.00040-17.（封面文章）
19. Wang Y*, Shen Y*, Dai Q, Yang Q, Zhang Y, Wang X, Xie W, Luo Z†, Lin C †. A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron. Nucleic Acids Res. 2017 Feb 17;45(3):1177-1185.
20. Luo Z, Lin C†. Enhancer, epigenetics and human diseases. Curr Opin Genet Dev. 2016 Apr 21;36:27-33.
21. Luo Z, Lin C, Ashley RW, Bartom E, Gao X, Smith E, and Shilatifard A. Regulation of imprinted gene expression by allele-specific enhancer activity. Genes Dev. 2016 Jan 1;30(1):92-101.
22. De Kumar B, Parrish ME, Slaughter BD, Unruh JR, Gogol M, Seidel C, Paulson A, Li H, Gaudenz K, Peak A, McDowell W, Fleharty B, Ahn Y, Lin C, Smith E, Shilatifard A, Krumlauf R. Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells. Genome Res. 2015 Aug;25(8):1229-43.
23. Luo Z, Gao X, Lin C, Smith ER, Marshall SA, Swanson SK, Florens L, Washburn MP, Shilatifard A. Zic2 is an enhancer-binding factor required for embryonic stem cell specification. Mol Cell. 2015 Feb 19;57(4):685-94.
24. Hu D, Smith ER, Garruss AS, Mohaghegh N, Varberg JM, Lin C, Jackson J, Gao X, Saraf A, Florens L, Washburn MP, Eissenberg JC, Shilatifard A. The little elongation complex functions at initiation and elongation phases of snRNA gene transcription. Mol Cell. 2013 Aug 22;51(4):493-505.
25. Lin C, Garrus AS, Luo Z, Guo F, Shilatifard A. The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation. Cell. 2013 Jan 17;152(1-2):144-56.
26. Luo Z, Lin C, Shilatifard A. The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol. 2012 Aug 16;13(9):543-7.
27. Luo Z, Lin C, Guest E, Garrett AS, Mohaghegh N, Swanson S, Marshall S, Florens L, Washburn MP, Shilatifard A. The super elongation complex family of RNA polymerase II elongation factors: gene target specificity and transcriptional output. Mol Cell Biol. 2012 Jul;32(13):2608-17.
28. Smith ER, Lin C, Garrett AS, Thornton J, Mohaghegh N, Hu D, Jackson J, Saraf A, Swanson SK, Seidel C, Florens L, Washburn MP, Eissenberg JC, Shilatifard A. The little elongation complex regulates small nuclear RNA transcription. Mol Cell. 2011 Dec 23;44(6):954-65.
29. Lin C, Garrett AS, De Kumar B, Smith ER, Gogol M, Seidel C, Krumlauf R, Shilatifard A. Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes Dev. 2011 Jul 15;25(14):1486-98. （封面亮点文章介绍）
30. Takahashi H, Parmely TJ, Sato S, Tomomori-Sato C, Banks CA, Kong SE, Szutorisz H, Swanson SK, Martin-Brown S, Washburn MP, Florens L, Seidel CW, Lin C, Smith ER, Shilatifard A, Conaway RC, Conaway JW. Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell. 2011 Jul 8;146(1):92-104.
31. Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 2011 Apr 1;25(7):661-72.
32. Mohan M, Lin C, Guest E, Shilatifard A. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer. 2010 Oct;10(10):721-8.
33. Mohan M, Herz HM, Takahashi YH, Lin C, Lai KC, Zhang Y, Washburn MP, Florens L, Shilatifard A. Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev. 2010 Mar 15;24(6):574-89.
34. Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010 Feb 12;37(3):429-37. （同期杂志述评）(Recommended by the Faculty of 1000)
35. Wang P, Lin C, Smith ER, Guo H, Sanderson BW, Wu M, Gogol M, Alexander T, Seidel C, Wiedemann LM, Ge K, Krumlauf R, Shilatifard A. Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Mol Cell Biol. 2009 Nov;29(22):6074-85
36. Lin C, Yuan YA. Structural insights into histone H3 lysine 56 acetylation by Rtt109. Structure. 2008 Oct 8;16(10):1503-10. （封面文章）
37. Chen HY, Yang J, Lin C, Yuan YA. Structural basis for RNA-silencing suppression by Tomato aspermy virus protein 2b. EMBO Rep. 2008 Aug;9(8):754-60.
