林承棋教授，博士生導(dǎo)師
個(gè)人簡(jiǎn)介：
林承棋，二級(jí)教授，首席教授，博士生導(dǎo)師，國家級(jí)青年人才，國家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目首席科學(xué)家，國家級(jí)高層次人才。主要研究方向：1、基因表達(dá)調(diào)控機(jī)制；2、細(xì)胞命運(yùn)決定與早期胚胎發(fā)育調(diào)控。在Cell、Nature Cell Biology、Molecular Cell、Cell Death and Differentiation、Genes & Development、Science Advances等雜志發(fā)表SCI論文30 余篇，引用4000余篇次?，F(xiàn)主持國家重點(diǎn)研發(fā)項(xiàng)目、基金委重點(diǎn)項(xiàng)目及面上項(xiàng)目。曾獲新加坡國家醫(yī)學(xué)研究理事會(huì)(NMRC)轉(zhuǎn)化與臨床研究、新加坡衛(wèi)生部物醫(yī)藥研究理事會(huì)(BMRC)項(xiàng)目、江蘇省杰出青年基金，江蘇省“雙創(chuàng)人才“等多項(xiàng)基金資助。
教育和工作簡(jiǎn)歷：
1998至2003年，東南大學(xué)，臨床醫(yī)學(xué)，學(xué)士
2003至2006年，東南大學(xué)，遺傳學(xué)，碩士
2006至2008年，新加坡國立大學(xué)，研究助理
2008至2013年，美國Stowers Institute for Medical Research，分子與細(xì)胞生物學(xué)，博士
2013至2016年，新加坡Institute of Molecular and Cell Biology，A-STAR，Young Investigator
2016至今，東南大學(xué)，生命科學(xué)與技術(shù)學(xué)院，教授
研究方向：
1.【基因表達(dá)調(diào)控機(jī)制】
基因表達(dá)調(diào)控是細(xì)胞生命活動(dòng)的基礎(chǔ)?；虿町愋员磉_(dá)在細(xì)胞命運(yùn)決定、個(gè)體發(fā)育以及疾病的發(fā)生發(fā)展中起到?jīng)Q定性作用。RNA 聚合酶 II（Pol II）啟動(dòng)子近端暫停是一種進(jìn)化上保守、從細(xì)菌到人類普遍存在的基因表達(dá)調(diào)控機(jī)制；其在早期胚胎發(fā)育、免疫反應(yīng)、應(yīng)激反應(yīng)等生命過程中發(fā)揮重要作用。實(shí)驗(yàn)室在國際上首次鑒定了超級(jí)轉(zhuǎn)錄延伸復(fù)合物Super Elongation Complex (SEC) SEC 可通過磷酸化 Pol II， SPT5 及 NELF，促進(jìn) Pol II 從暫停狀態(tài)進(jìn)入有效轉(zhuǎn)錄延伸階段，進(jìn)而調(diào)控機(jī)體應(yīng)激及發(fā)育相關(guān)基因的快速協(xié)調(diào)性轉(zhuǎn)錄激活。（Molecular Cell, 2010；Genes&Development, 2011；Cell, 2013）。近期的研究發(fā)現(xiàn)，SEC介導(dǎo)的多價(jià)相分離在RNA聚合酶II轉(zhuǎn)錄暫停釋放中起著關(guān)鍵作用，并從全新的角度為基因快速協(xié)調(diào)性轉(zhuǎn)錄激活程序的機(jī)制探索提供了新的認(rèn)識(shí)（Science Advance,2020；EMBO reports,2023）。實(shí)驗(yàn)室將繼續(xù)致力于基因轉(zhuǎn)錄調(diào)控的新機(jī)制探究，及其失調(diào)如何驅(qū)動(dòng)疾病發(fā)生發(fā)展。
增強(qiáng)子可以跨越遠(yuǎn)距離基因組序列，精準(zhǔn)的在時(shí)間和空間上控制基因表達(dá)。因此，增強(qiáng)子精準(zhǔn)匹配靶標(biāo)啟動(dòng)子，是基因調(diào)控網(wǎng)絡(luò)研究的重中之重。近年來，增強(qiáng)子表觀遺傳學(xué)研究表明在胚胎發(fā)育早期階段存在多種不同狀態(tài)的增強(qiáng)子來維持其多向分化潛能。目前對(duì)于處于暫?；蚴Щ顮顟B(tài)的增強(qiáng)子的功能尚不清楚。課題組在國際上首次報(bào)道轉(zhuǎn)錄延伸因子ELL3可結(jié)合在暫停狀態(tài)的啟動(dòng)子上，調(diào)控RNA Pol II暫停，進(jìn)而調(diào)控增強(qiáng)子的活性及干細(xì)胞多能性（Cell，2013）；近期的研究，進(jìn)一步發(fā)現(xiàn)ELL3結(jié)合的L1NE-1 5’UTR可作為一類全新的增強(qiáng)子元件，調(diào)控早期胚胎發(fā)育，其功能異常將會(huì)導(dǎo)致胚胎發(fā)育缺陷、流產(chǎn)（Nat Cell Biol, 2023，封面文章）。我們將進(jìn)一步探究增強(qiáng)子-啟動(dòng)中互作的特異性，及其介導(dǎo)的基因表達(dá)特異性在干細(xì)胞多向分化潛能和早期胚胎發(fā)育中的作用和分子機(jī)理。
2.【細(xì)胞命運(yùn)決定與早期胚胎發(fā)育調(diào)控】
細(xì)胞命運(yùn)決定貫穿發(fā)育和疾病全過程，其核心是基因差異性表達(dá)。合子基因組激活(human zygotic genome activation, ZGA)作為啟動(dòng)胚胎發(fā)育進(jìn)程的關(guān)鍵事件，標(biāo)志著受精后基因表達(dá)的起始，這一過程取決于RNA聚合酶II對(duì)合子基因組啟動(dòng)子的有序識(shí)別，同時(shí)也受到染色質(zhì)的結(jié)構(gòu)和轉(zhuǎn)錄因子的協(xié)同調(diào)控。我們將進(jìn)一步探究合子基因組激活的轉(zhuǎn)錄及表觀遺傳調(diào)控機(jī)理；其次，明確ZGA對(duì)胚胎全能性、多能性及胚層發(fā)育的影響及調(diào)控機(jī)制；同時(shí)探究早期胚胎發(fā)育過程中轉(zhuǎn)座元件的意外作用。本研究將豐富人們對(duì)早期胚胎發(fā)育、合子基因組激活等方面的生物學(xué)機(jī)制的認(rèn)識(shí)；對(duì)輔助生殖、優(yōu)生優(yōu)育等的基礎(chǔ)生物學(xué)研究和臨床診療也具有重要的指導(dǎo)價(jià)值。
心臟是第一個(gè)形成的器官。其形成與再生異常，可分別導(dǎo)致先天性心臟病和成人心臟病。先天性心臟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(wèi)生問題。大量研究顯示，胚胎時(shí)期心臟發(fā)育異常是導(dǎo)致先天性心臟缺陷的主要原因。在早期心臟發(fā)育過程中，心臟前體細(xì)胞的動(dòng)態(tài)演化路徑是什么？心臟細(xì)胞存在哪些不同的分化來源？不同來源的心臟前體細(xì)胞受到哪些關(guān)鍵的轉(zhuǎn)錄因子與基因組調(diào)控元件的影響？這些問題的解答對(duì)于我們理解心臟早期發(fā)育過程，進(jìn)而治療心臟發(fā)育疾病至關(guān)重要。
代表性論文：（?通訊作者）
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 na?ve 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. （同期雜志述評(píng)）
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. （同期雜志述評(píng)）
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. （封面亮點(diǎn)文章介紹）
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. （同期雜志述評(píng)）(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.
