染色质与表观遗传学系列讲座2023年 第2场 – Antonio Giraldez

主讲人 | Speaker Antonio Giraldez 主讲人简介 | Speaker Biography Antonio教授在加的斯大学和马德里自治大学学习化学和分子生物学。本科期间，他在马德里的CBM与Gines Morata一起工作。Antonio教授在EMBL (海德堡) 师从斯蒂芬·科恩 (Stephen Cohen ，1998-2002) 获得博士学位，并在Skirball研究所(纽约大学)和哈佛大学 (2003-2006) 师从亚历克斯·席尔 (Alex Schier) 做博士后工作。2007年， Antonio教授在耶鲁大学成立了自己的实验室，他在那里研究胚胎发育过程中影响基因表达的调控密码。他是研究生研究主任(2012-2016)，目前是遗传学系主任(2017-)。 Antonio studied Chemistry and Molecular Biology at the University of Cadiz and the University Autonoma of Madrid. During undergraduate, he worked with Gines Morata at the CBM in Madrid. Antonio did his PhD with Stephen Cohen at the EMBL (Heidelberg) (1998-2002) and a post-doc with Alex Schier at the Skirball Institute (NYU) and Harvard (2003-2006). Antonio established his laboratory at Yale in 2007 where he investigates the regulatory codes that shape gene expression during embryonic development. He was Director of Graduate Studies (2012-2016) and is currently Chair of the Genetics Department (2017- ). 报告标题 | Title Expanding our view of genome activation using genomics and expansion microscopy 报告摘要 | Abstract Development begins with a single-cell zygote, the product of the union of sperm and oocyte. Upon fertilization, the zygotic genome undergoes extensive developmental reprogramming during the Maternal-to-Zygotic transition (MZT), which confers a totipotent state upon the zygote. This universal step in animal development results in the activation of the zygotic genome, the reprogramming of maternally inherited regulators, and the initiation of embryonic development. My laboratory investigates the mechanisms that regulate the activation of the genome and the post-transcriptional regulation of the maternal mRNAs with the goal of drawing common principles in biology. In this seminar, I will present our recent research on the mechanisms that control genome activation and the sequence of events that dictate chromatin reprogramming to establish developmental competency during genome activation. In the second part, I will describe our new efforts to visualize the process of transcriptional regulation and epigenetics remodeling using iterative expansion microscopy. This allows us to expand the samples 15 fold in a linear manner and 4000 fold in volume while retaining most proteins. This allows us to visualize important processes of gene regulation with 3-15 nm resolution while maintaining protein retention. The results presented will provide insights into the sequence of events that mediate developmental reprogramming during genome activation. 主讲人近年发表论文摘选 | Selected Recent Publications 1. Miao L, Tang Y, Bonneau AR, Chan SH, Kojima ML, Pownall ME, Vejnar CE, Gao F, Krishnaswamy S, Hendry CE, Giraldez AJ. The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation. Mol Cell. 2022 Mar 3;82(5):986-1002.e9. doi: 10.1016/j.molcel.2022.01.024. Epub 2022 Feb 18. PMID: 35182480; PMCID: PMC9327391. 2. Vejnar CE, Abdel Messih M, Takacs CM, Yartseva V, Oikonomou P, Christiano R, Stoeckius M, Lau S, Lee MT, Beaudoin JD, Musaev D, Darwich-Codore H, Walther TC, Tavazoie S, Cifuentes D, Giraldez AJ. Genome wide analysis of 3' UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish. Genome Res. 2019 Jul;29(7):1100-1114. doi: 10.1101/gr.245159.118. Epub 2019 Jun 21. PMID: 31227602; PMCID: PMC6633259. 3. Chan SH, Tang Y, Miao L, Darwich-Codore H, Vejnar CE, Beaudoin JD, Musaev D, Fernandez JP, Benitez MDJ, Bazzini AA, Moreno-Mateos MA, Giraldez AJ. Brd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation. Dev Cell. 2019 Jun 17;49(6):867-881.e8. doi: 10.1016/j.devcel.2019.05.037. PMID: 31211993; PMCID: PMC7201981. 4. Beaudoin JD, Novoa EM, Vejnar CE, Yartseva V, Takacs CM, Kellis M, Giraldez AJ. Analyses of mRNA structure dynamics identify embryonic gene regulatory programs. Nat Struct Mol Biol. 2018 Aug;25(8):677-686. doi: 10.1038/s41594-018-0091-z. Epub 2018 Jul 30. PMID: 30061596; PMCID: PMC6690192. 5. Bazzini AA, Del Viso F, Moreno-Mateos MA, Johnstone TG, Vejnar CE, Qin Y, Yao J, Khokha MK, Giraldez AJ. Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition. EMBO J. 2016 Oct 4;35(19):2087-2103. doi: 10.15252/embj.201694699. Epub 2016 Jul 19. PMID: 27436874; PMCID: PMC5048347. 6. Johnstone TG, Bazzini AA, Giraldez AJ. Upstream ORFs are prevalent translational repressors in vertebrates. EMBO J. 2016 Apr 1;35(7):706-23. doi: 10.15252/embj.201592759. Epub 2016 Feb 19. PMID: 26896445; PMCID: PMC4818764. 7. Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK, Giraldez AJ. CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods. 2015 Oct;12(10):982-8. doi: 10.1038/nmeth.3543. Epub 2015 Aug 31. PMID: 26322839; PMCID: PMC4589495. 8. Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK, Giraldez AJ. CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods. 2015 Oct;12(10):982-8. doi: 10.1038/nmeth.3543. Epub 2015 Aug 31. PMID: 26322839; PMCID: PMC4589495. 9. Bazzini AA, Johnstone TG, Christiano R, Mackowiak SD, Obermayer B, Fleming ES, Vejnar CE, Lee MT, Rajewsky N, Walther TC, Giraldez AJ. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 2014 May 2;33(9):981-93. doi: 10.1002/embj.201488411. Epub 2014 Apr 4. PMID: 24705786; PMCID: PMC4193932. 10. Lee MT, Bonneau AR, Takacs CM, Bazzini AA, DiVito KR, Fleming ES, Giraldez AJ. Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Nature. 2013 Nov 21;503(7476):360-4. doi: 10.1038/nature12632. Epub 2013 Sep 22. PMID: 24056933; PMCID: PMC3925760. 11. Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson ND, Wolfe SA, Giraldez AJ. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science. 2010 Jun 25;328(5986):1694-8. doi: 10.1126/science.1190809. Epub 2010 May 6. PMID: 20448148; PMCID: PMC3093307. 12. Bazzini AA, Lee MT, Giraldez AJ. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science. 2012 Apr 13;336(6078):233-7. doi: 10.1126/science.1215704. Epub 2012 Mar 15. PMID: 22422859; PMCID: PMC3547538. 13. Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 2006 Apr 7;312(5770):75-9. doi: 10.1126/science.1122689. Epub 2006 Feb 16. PMID: 16484454. 14. Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005 May 6;308(5723):833-8. doi: 10.1126/science.1109020. Epub 2005 Mar 17. PMID: 15774722. 本活动由Active Motif赞助 Sponsored by: Active Motif 中国细胞生物学学会