林承棋教授，博士生導師
個人簡介：
林承棋，二級教授，青年首席教授，博士生導師，國家級青年人才，國家重點研發計劃項目首席科學家，“萬人計劃”中青年科技創新領軍人才。主要研究方向：1、基因表達調控機制；2、細胞命運決定與早期胚胎發育調控。在Cell、Nature Cell Biology、Molecular Cell、Cell Death and Differentiation、Genes & Development、Science Advances等雜志發表SCI論文30 餘篇，引用4000餘篇次。現主持國家重點研發項目、基金委重點項目及面上項目。曾獲新加坡國家醫學研究理事會(NMRC)轉化與臨床研究、新加坡衛生部物醫藥研究理事會(BMRC)項目、江蘇省傑出青年基金，江蘇省“雙創人才“等多項基金資助。
教育和工作簡曆：
1998至2003年，bet356在线官方网站，臨床醫學，學士
2003至2006年，bet356在线官方网站，遺傳學，碩士
2006至2008年，新加坡國立大學，研究助理
2008至2013年，美國Stowers Institute for Medical Research，分子與細胞生物學，博士
2013至2016年，新加坡Institute of Molecular and Cell Biology，A-STAR，Young Investigator
2016至今，bet356在线官方网站，beat365体育官网平台，教授
研究方向：
1.【基因表達調控機制】
基因轉錄是承載于DNA之上遺傳信息傳遞的首要步驟。轉錄差異導緻的基因差異性表達在細胞命運決定、個體發育以及疾病的發生發展中起到決定性作用。實驗室長期緻力于探究基因表達的轉錄調控機制，在國際上首次鑒定了細胞命運決定關鍵的轉錄因子複合體Super Elongation Complex (SEC)，發現其通過調控RNA聚合酶II暫停釋放，介導相分離等多種機制影響基因轉錄，介導重要生物學進程。實驗室将繼續緻力于基因轉錄調控的機制探究，理解和完善基因轉錄調控的模式。
增強子可以跨越遠距離基因組序列，精準的在時間和空間上控制基因表達。因此，增強子精準匹配靶标啟動子，是基因調控網絡研究的重中之重。近年來，增強子表觀遺傳學研究表明在胚胎發育早期階段存在多種不同狀态的增強子來維持其多向分化潛能。目前對于處于暫停或失活狀态的增強子的功能尚不清楚。我們将進一步探究SEC及其他增強子特異結合因子在幹細胞自我更新和多向分化潛能調控中的功能和分子機理。
2.【細胞命運決定與早期胚胎發育調控】
細胞命運決定貫穿發育和疾病全過程，其核心是基因差異性表達。合子基因組激活(human zygotic genome activation,ZGA)作為啟動胚胎發育進程的關鍵事件，标志着受精後基因表達的起始，這一過程取決于RNA聚合酶II對合子基因組啟動子的有序識别，同時也受到染色質的結構和轉錄因子的協同調控。我們将進一步探究合子基因組激活的轉錄及表觀遺傳調控機理；其次，明确ZGA對胚胎全能性、多能性及胚層發育的影響及調控機制；同時探究早期胚胎發育過程中轉座元件的意外作用。本研究将豐富人們對早期胚胎發育、合子基因組激活等方面的生物學機制的認識；對輔助生殖、優生優育等的基礎生物學研究和臨床診療也具有重要的指導價值。
心髒是第一個形成的器官。其形成與再生異常，可分别導緻先天性心髒病和成人心髒病。先天性心髒病是我國最常見的出生缺陷，約占28%，是影響我國新生人口健康的重大公共衛生問題。大量研究顯示，胚胎時期心髒發育異常是導緻先天性心髒缺陷的主要原因。在早期心髒發育過程中，心髒前體細胞的動态演化路徑是什麼？心髒細胞存在哪些不同的分化來源？不同來源的心髒前體細胞受到哪些關鍵的轉錄因子與基因組調控元件的影響？這些問題的解答對于我們理解心髒早期發育過程，進而治療心髒發育疾病至關重要。
代表性論文：（†通訊作者）
1. 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）
2. 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.
3. 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. （同期雜志述評）
4. Guo C, Luo Z†, Lin C†. Phase Separation Properties in Transcriptional Organization. Biochemistry. 2022 Nov 15;61(22):2456-2460.
5. 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.
6. 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.
7. 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）
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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. （同期雜志述評）
14. 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.
15. 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.
16. 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）
17. 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.
18. Luo Z, Lin C†. Enhancer, epigenetics and human diseases. Curr Opin Genet Dev. 2016 Apr 21;36:27-33.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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. （封面亮點文章介紹）
28. 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.
29. 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.
30. 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.
31. 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.
32. 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. （同期雜志述評）(Recommended by the Faculty of 1000)
33. 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
34. 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）
35. 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.
