羅卓娟教授,博士生導師
羅卓娟,青年首席教授,博士生導師,國家級青年人才。主要研究方向:表觀遺傳學、細胞生物學、癌症生物學。主要研究内容:1、基因表達調控機制;2、基因印記調控機制;3、表觀遺傳與疾病發生發展。在Nature Reviews Molecular Cell Biology、Nature Cell Biology、Molecular Cell、Cell Death and Differentiation、Genes & Development、Science Advances等雜志發表SCI論文20 餘篇。主持國家自然基金面上項目、江蘇省傑出青年基金、江蘇省“雙創人才”等項目。參與國家重點研發計劃、江蘇省“雙創團隊”等項目。
教育和工作簡曆:
1998至2002年,安徽大學,學士
2002至2005年,bet356在线官方网站,碩士
2006至2011年,新加坡國立大學,博士
2011至2015年,美國Stowers Institute for Medical Research,博士後
2015年, Feinberg School of Medicine, Northwestern University,博士後
2016至今,bet356在线官方网站,beat365体育官网平台,教授
研究方向:
1. 【染色質結構調控基因表達的功能機制】
DNA包裹組蛋白形成的染色質結構是基因表達的基本元件,長久以來認為DNA序列本身決定了基因的表達。然而,近年來發現,染色質二級結構也可以調控基因轉錄。染色質的二級結構,主要包括DNA二級結構,DNA-RNA雜交的二級結構等。染色質二級結構在不同的組織和階段受到特異性調控,在基因序列之外影響轉錄和細胞命運決定。研究其特異性調控對于理解不同細胞間的轉錄調控和命運切換具有重要意義。實驗室在國際上首次鑒定了ZEBRAQ(ZNF281,BRCA2,EMSY,QSER1)複合物,并發現其通過調控染色質的DNA-RNA雜交三鍊結構R-loop(R環),影響基因轉錄,介導重要生物學進程。實驗室将繼續緻力于染色質結構介導基因轉錄調控的機制探究。
2.【基因印記與X染色體失活調控機制】
基因組印記是一種非孟德爾式的特殊遺傳現象,受印記調控的基因(印記基因)呈父或母源特異性單拷貝表達。印記基因對于個體的生長發育起到至關重要的作用,其異常會導緻嚴重的多器官發育缺陷、智力障礙以及惡性腫瘤,如Angelman綜合征、Beckwith-Wiedemann 綜合征及Prader-Willi 綜合征。一直以來,表觀遺傳,包括DNA甲基化以及組蛋白H3K9甲基化,是調控基因組印記的唯一且經典機制。本實驗室前期的研究首次發現轉錄延伸因子AFF3可結合在抑制性的甲基化印記控制區ICR,在基因組印記調控中起到獨特的雙向調控作用。此外,AFF3在另外一類表觀遺傳現象,X染色體失活中也發揮獨特作用。近年來,全基因組關聯分析顯示AFF3是自體免疫性疾病,如類風濕性關節炎、I型糖尿病、紅斑狼瘡等的易感因子。
本實驗室在多種疾病與發育模型中來探索基因組印記與X染色體失活的調控,這将為我們提供一個很好的模型來深入解析印記基因在發育與疾病中的調控機理,為印記基因參與重大疾病發生發展提供新思路與新認識。
3.【表觀遺傳與疾病發生發展】
癌症等疾病的産生是諸多遺傳因素共同作用的結果,除了基因突變外,表觀遺傳學變化導緻的轉錄調控遺傳也被認為是癌症産生的重要因素。研究癌症表觀遺傳調控,可以溯源癌症的發生過程、指針癌症的惡性程度、尋找癌症新的治療靶标。實驗室前期發現ZEBRAQ複合物通過轉錄調控、表觀遺傳修飾調控等多種方式影響惡性腫瘤疾病進程。我們将進一步探究表觀遺傳調控異常和疾病發生發展的關系,以期尋找潛在的癌症分子治療靶标。
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. 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.
11. 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.
12. 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)
13. 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.
14. 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)
15. 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.
16. Luo Z, Lin C†. Enhancer, epigenetics and human diseases. Curr Opin Genet Dev. 2016 Apr 21;36:27-33.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.