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北京时间2021年1月19日(周二) 21:00-22:00
2021 Jan 19th Tuesday 21:00-22:00 (Beijing Time)
参与方式 | Location
Zoom网络研讨会: 843 6931 3262
Bilibili直播:http://live.bilibili.com/22741871
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主讲人 | Speaker
Yi Zhang
主讲人简介 | Speaker Biography
张毅教授是霍华德·休斯医学院的研究员,同时也是哈佛医学院和波士顿儿童医院遗传学Fred Rosen讲席教授。他在佛罗里达州州立大学分子生物物理研究所取得博士学位,其间研究锤头状核酶。随后,他在新泽西医科和牙科大学(UMDNJ)的罗伯特·伍德·约翰逊医学院(Robert Wood Johnson Medical School)进行了博士后培训,在那里他鉴定并表征了多种组蛋白脱乙酰基酶复合物,包括Sin3和NuRD复合物。
他于1999年在北卡罗莱纳大学教堂山分校的莱恩伯格综合癌症中心(Lineberger Comprehensive Cancer Center)成立自己的实验室,于2005年成为霍华德·休斯研究员,并于2009年成为Kenan杰出教授。2012年8月,他将实验室搬迁至哈佛大学医学院和波士顿儿童医院。
Dr. Yi Zhang is currently an Investigator of the Howard Hughes Medical Institute, and the Fred Rosen Chair Professor of Genetics at Harvard Medical School and Boston Children’s Hospital. He obtained his Ph.D. from the Institute of Molecular Biophysics at Florida State University, where he studied the "hammerhead" ribozyme. His postdoctoral training was at the Robert Wood Johnson Medical School of UMDNJ where he identified and characterized several histone deacetylase complexes including the Sin3 and NuRD complexes.
He became an independent investigator at the Lineberger Comprehensive Cancer Center of the University of North Carolina at Chapel Hill in 1999, a Howard Hughes Investigator in 2005, and the Kenan Distinguished Professor in 2009. In August of 2012, he moved his laboratory to Harvard Medical School and Boston Children's Hospital.
报告标题 | Title
Distinct dynamics and functions of H2Aub and H3K27me3 in mouse pre-implantation development
报告摘要 | Abstract
Polycomb group (PcG) proteins play important roles in multiple biological processes including maintaining transcriptional silencing of developmental genes, regulating the balance of stem cell renewal and differentiation, and contributing to cancer. PcG proteins function in two major enzymatic complexes Polycomb repressive complex 1 and 2 (PRC1/2), which catalyze H2AK119ub (H2Aub) and H3K27me3, respectively. Studies in embryonic stem cells suggest that the two PcG complexes function together to silence differentiation genes to maintain pluripotency. However, genetic studies in mice indicated that the two complexes may not always function together as disruption of the two enzymatic activities resulted in different developmental phenotypes. Our recent studies revealed that maternal H3K27me3 can serve as a mark for genomic imprinting. It is not clear whether H2Aub is involved in this non-canonical imprinting. Furthermore, analysis of H3K27me3 in preimplantation embryos revealed unusual H3K27me3 domains, suggesting unique PcG regulations in mammalian early development. It is not clear whether H2Aub follows similar reprogramming dynamics as H3K27me3 after fertilization. To address all these questions, we performed genome wide H2Aub profiling during mouse early embryonic development and show that H2Aub, although highly overlapped with H3K27me3 in gametes, undergoes reprogramming with different dynamics from that of H3K27me3 in pre-implantation embryos. Notably, while depletion of maternal Eed has limited effect on global H2Aub in early embryos, it disrupts allelic H2Aub at the maternal H3K27me3-dependent non-canonical imprinting loci including Xist. In contrast, acute depletion of H2Aub in zygotes does not affect the maternally inherited H3K27me3 domains nor the imprinted expression of the associated genes at least by 4-cell stage, suggesting that H2Aub may not be required for non-canonical imprinting maintenance. Importantly, loss of H2Aub, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation and subsequent embryonic arrest. Thus, our study not only reveals distinct dynamics and functions of H3K27me3 and H2Aub in mouse pre-implantation embryos, but also highlights the complex and context specific PcG activities.
主讲人发表论文摘选
Selected Publications
1) Inoue, A., Jiang, L., Lu, F., Suzuki, T., and Zhang, Y. (2017). Maternal H3K27me3 controls DNA methylation-independent genomic imprinting. Nature 547, 419-424. PMID: 28723896
2) Matoba, S., Wang, H., Jiang, L., Lu, F., Iwabuchi, K.A., Wu, X., Inoue, K., Yang, L., Press, W., Lee, J.T., Ogura, A., Li, S., and Zhang, Y., (2018). Loss of H3K27me3 imprinting in somatic cell nuclear transfer embryos disrupts post-implantation development. Cell Stem Cell 23, 343-354. PMID: 30033120
3) Chen, Z., Yin, Q., Inoue, A., Zhang, C., and Zhang, Y. (2019). Allelic H3K27me3 to allelic DNA methylation switch maintains non-canonical imprinting in extraembryonic cells. Science Advances 5(12):eaay7246. PMID: 32064321
4) Fu, X., Wu, X., Djekidel, M.N., and Zhang, Y. (2019). Myc and Dnmt1 impede pluripotent to totipotent state transition in embryonic stem cell. Nature Cell Biol 21, 835-844. PMID: 31209294
5) Fu, X., Djekidel, M.N., Chen, Z., Zhang, Y. (2020). A transcriptional roadmap for 2C-like to pluripotent state transition. Science Advances 6(22):eaay5181. PMID: 32523982
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