林承棋

發布者：許峰發布時間：2019-08-14浏覽次數：31332

 

  林承棋 教授

  教育和工作簡曆

   1998至2003年，東南大學，臨床醫學，學士 
   2003至2006年，東南大學，遺傳學，碩士 
   2006至2008年，新加坡國立大學，研究助理 
   2008至2013年，Stowers Institute for Medical Research，分子與細胞生物學，博士
   2013至今，東南大學，生命科學院研究院，教授 


研究方向：轉錄調控在發育及疾病發生發展中的作用機理

多能胚胎幹細胞（pluripotent embryonic stem Cells）因其自我更新（self-renewal）及全能分化的潛力，成為再生醫學領域治療退行性疾病的基礎。如何高效安全特異地分化胚胎幹細胞成特殊的成熟細胞是當今的主要研究熱點之一，也是制約其臨床應用的主要瓶頸之一。本實驗室主要集中在轉錄延伸調控以及增強子表觀遺傳學領域來探索胚胎幹細胞維持其自我更新以及多向分化潛能的分子機理，以及轉錄延伸調控因子以及增強子突變在疾病發生發展中的作用機理。


1. 超級延伸複合物（SEC）在發育及疾病發生發展中的作用機理；

超級延伸複合物Super Elongation Complex (SEC) 調控着基因的快速協調性表達，在胚胎幹細胞定向分化中發揮着重要作用。SEC的異常激活是引起嬰幼兒白血病、HIV以及CHOP syndrome的主要原因之一。除了SEC，SEC類似複合物SEC

L2和－L3也在發育及疾病的發生發展中起到非常重要的作用。本課題将運用生化學、細胞生物學、基因組學以及表觀遺傳學手段探尋SEC及SEC

L如何差異性地調控胚胎幹細胞分化，以及它們在疾病中的特異性作用。


2. SEC相關增強子結合因子在維持胚胎幹細胞自我更新以及多向分化潛能的分子機理；

增強子(enhancer)是指一段可以通過與激活蛋白的結合增強其連鎖基因轉錄水平的DNA序列，其對于發育相關基因的時空特異性表達起到了關鍵性的作用。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。本課題将運用生化學、遺傳學以及基因組學手段探尋ELL3相關pioneer factors如何通過調控增強子活性和染色質可塑性來維持胚胎幹細胞自我更新和多向分化潛能的分子機理。


近期代表性論文：


  1.  Guo C H, Luo Z J†, Lin C Q†. Dynamic regulation of promoter-proximal RNA polymerase II pausing (in Chinese). Chin Sci Bull, 2020, 65: 1–1, doi: 10.1360/ TB-2020-0581

  2.  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:mjaa061. 

  3.  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.

  1.  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.

  2.  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. doi: 10.1128/MCB.00329-19.

  3.  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.

  4.  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.

  5.  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. doi: 10.1093/nar/gkx841.

  6.  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. doi: 10.1128/MCB.00040-17.

  7.  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.

  8.  Luo Z, Lin C†. Enhancer, epigenetics and human diseases. Curr Opin Genet Dev.2016 Apr 21;36:27-33.

  9.  Regulation of imprinted gene expression by allele-specific enhancer activity. Luo Z, Lin C, Ashley RW, Bartom E, Gao X, Smith E, and Shilatifard A. Genes Dev. 2016 Jan 1;30(1):92-101.

  10.  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.

  11.  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.

  12.  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.

  13. 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.

  14.  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.

  15.  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.

  16.  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.

  17. 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.

  18.  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.

  19.  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.

  20.  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.

  21.  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.

  22. 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. (Recommended by the Faculty of 1000)

  23.  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

  24. Lin C, Yuan YA. Structural insights into histone H3 lysine 56 acetylation by Rtt109.Structure. 2008 Oct 8;16(10):1503-10. (Cover paper)

  25.  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.









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