染色质与表观遗传学系列讲座第22场 – Dirk Schübeler

发布日期：2022-01-14　　浏览次数：30409

活动时间 | Time

北京时间2022年1月18日（周二） 20:00-21:00

2022 January 4th Tuesday 20:00-21:00 (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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Webinar ID: 843 6931 3262

Bilibili Live: http://live.bilibili.com/22741871

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主讲人 | Speaker

Dirk Schübeler

主讲人简介 | Speaker Biography

Dr. Dirk Schübeler is Director of the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel, Switzerland, as well as Professor of Molecular Biology at the University of Basel. He received a PhD from the Technical University in Braunschweig, Germany, and worked as a postdoctoral fellow at the Fred Hutchinson Cancer Center in Seattle, USA.

Dirk Schübeler’s research focuses on understanding how chromatin states are generated and how they contribute to the regulation of transcription and replication. His group has pioneered approaches to measure DNA methylation, histone modifications and DNA replication at the level of the genome and to combine these with functional assays. The group has identified recruitment mechanism for readers and writers of DNA methylation towards a better understanding of the information flow that generates and reads a chromatinized genome. In more recent work his group aims to define how transcription factors respond and modify chromatin.

Dirk Schübeler is a member of EMBO. He received several awards, including the Friedrich Miescher Prize of the Swiss Society for Biochemistry and the Novartis VIVA award, and three ERC grants.

Dirk Schübeler教授是瑞士弗雷德里希·米歇尔生物医学研究所（Friedrich Miescher Institute for Biomedical Research，FMI）主任、巴塞尔大学分子生物学教授。他在德国布伦瑞克工业大学获得博士学位，并在美国西雅图的弗雷德·哈钦森癌症研究中心（Fred Hutchinson Cancer Research Center）担任博士后研究员。Dirk Schübeler教授的重点研究方向是染色质状态的形成，以及它们如何参与调节转录和复制。他的研究组开创了在基因组水平上测量DNA甲基化、组蛋白修饰和DNA复制的方法，并将这些方法与功能分析相结合。研究组确定了DNA甲基化的读取者（reader）和写入者（wrtiter）的招募机制，从而更好地理解染色质化基因组的形成和读取的信息流。在最近的工作中，他的研究组的重点研究方向是转录因子如何响应和修饰染色质状态。Dirk Schübeler教授是欧洲分子生物学组织（EMBO）的成员。他曾获得多个奖项，包括瑞士生物化学学会的弗雷德里希·米歇尔奖和诺华VIVA 奖，以及三项欧洲研究委员会（ERC）基金资助。

报告标题 | Title

Beyond Motif: Guiding Sites of Transcription Factor Binding by DNA Modifications

报告摘要 | Abstract

Transcription factors only bind a minority of their motifs in large mammalian genomes. One potential explanation is that many motifs are not accessible for binding due to the action of chromatin and DNA methylation. We are using mammalian stem cell models to understand this important interplay between gene regulation, chromatin structure and DNA methylation. We study the dynamics of the epigenome and test regulatory models in cellular models by genetic perturbation and genome editing approaches.

I will discuss our recent efforts in understanding how DNA methylation represses regulatory regions and how the sensitivity to DNA methylation can limit transcription factor binding in the context of the cell.

主讲人发表论文摘选| Selected Publications

1) RS Grand*, L Burger*, C Gräwe, AK Michael, L Isbel, D Hess, L Hoerner, V Iesmantavicius, S Durdu, M Pregnolato, AR Krebs, SA Smallwood, N Thomä, M Vermeulen, D Schübeler (2021) BANP opens chromatin and activates CpG-island-regulated genes. Nature 596 (7870), 133-137

2) R Lopes, K Sprouffske, C Sheng, ECH Uijttewaal, AE Wesdorp, J Dahinden, S Wengert, J Diaz-Miyar, U Yildiz, M Bleu, V Apfel, F Mermet-Meillon, R Krese, M Eder, AV Olsen, P Hoppe, J Knehr, W Carbone, R Cuttat, A Waldt, M Altorfer, U Naumann, J Weischenfeldt, A DeWeck, A Kauffmann, G Roma, D Schübeler, GG Galli (2021) Systematic dissection of transcriptional regulatory networks by genome-scale and single-cell CRISPR screens. Science Advances 7 (27), eabf5733

3) M Iurlaro, MB Stadler, F Masoni, Z Jagani, GG Galli, D Schübeler (2021) Mammalian SWI/SNF continuously restores local accessibility to chromatin. Nature Genetics, 53, 279–287.

4) PA Ginno*, D Gaidatzis*, A Feldmann*, L Hoerner, D Imanci, L Burger, F Zilbermann, AHFM Peters, F Edenhofer, SA Smallwood, AR Krebs, D Schübeler (2020) A genome-scale map of DNA methylation turnover identifies site-specific dependencies of DNMT and TET activity. Nature Communications, 11(1):2680

5) AK Michael*, RS Grand*, L Isbel*, S Cavadini, Z Kozicka, G Kempf, RD Bunker, AD Schenk, A Graff-Meyer, GR Pathare, J Weiss, S Matsumoto, L Burger, D Schübeler, NH Thomä (2020) Mechanisms of OCT4-SOX2 motif readout on nucleosomes. Science, 368, 6498, 1460-1465

6) C Sönmezer, R Kleinendorst, D Imanci, G Barzaghi, L Villacorta, D Schübeler, V Benes, N Molina, AR Krebs (2020) Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo. Molecular Cell, 81 (2), 255-267. e6

7) J Juettner, A Szabo, B Gross-Scherf, RK Morikawa, SB Rompani, P Hantz, T Szikra, F Esposti, CS Cowan, A Bharioke, CP Patino-Alvarez, Ö Keles, A Kusnyerik, T Azoulay, D Hartl, AR Krebs, D Schübeler, RI Hajdu, A Lukats, J Nemeth, ZZ Nagy, K-C Wu, R-H Wu, L Xiang, X-L Fang, Z-B Jin, D Goldblum, PW Hasler, HPN Scholl, J Krol, B Roska (2019) Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans. Nature Neuroscience, 22 (8), 1345-1356

8) S Matsumoto, S Cavadini, RD Bunker, RS Grand, A Potenza, J Rabl, J Yamamoto, AD Schenk, D Schübeler, S Iwai, K Sugasawa, H Kurumizaka, NH Thomä (2019) DNA damage detection in nucleosomes involves DNA register shifting. Nature, 571, 79–84

9) D Barisic*, MB Stadler*, M Iurlaro*, D Schübeler (2019) Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors. Nature, 569 (7754), 136–140

10) D Hartl, AR Krebs, RS Grand, T Baubec, L Isbel, C Wirbelauer, L Burger and D Schubeler (2019) CG dinucleotides enhance promoter activity independent of DNA methylation. Genome Research 29, 554–563

往期回顾 | Past Webinars

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