报告题目：Genetic and structural investigations of DNA methylation maintenance mechanisms
报告人：Pierre-Antoine Defossez 巴黎第七大学
主持人：翁杰敏 教授
报告时间：2019年11月29日10:00（周五上午）
报告地点：生命科学学院534小会议室
报告人简介：
Current position | |||||||||
French public organisation | |||||||||
RNSR code | Organisation | Laboratory | Unit code | Postcode | Town | ||||
200918506F | Professor，CNRS/Univ Paris Diderotor
| Epigenetics and cell fate | 7216 | 75013 | Paris | ||||
Function | |||||||||
Group leader, DR2 CNRS, since 2009. | |||||||||
Other activities Executive board, supervision of student, teaching, memberships in panels or individual scientific reviewing activities | |||||||||
Associate professor, Ecole Polytechnique. Teaching activity at ENS Paris, ENS Cachan, and ENS Lyon. CNRS study section 21, member 2012-2015. Institut National du Cancer, PLBio evaluation committee, member in 2011, president in 2012 and 2017. Executive board, Labex “Who am I?” Reviewer for multiple national and international research agencies: HCERES, ANR, ARC, Ligue, INCa (France); Cancer Research UK, MRC, BBSRC (UK); NWO (Netherlands); FWF (Austria); CIHR (Canada). Ad hoc reviewer for: EMBO Journal, Genome Research, Elife, Nucleic Acids Research, Nature Communications, Cell Reports, Molecular Cell, Nature… | |||||||||
Previous positions | |||||||||
Start date | End date | Town | Organisation | Function | |||||
04/2003 | 12/2008 | Paris, France | Institut Curie, Department of Epigenetics (Head: Geneviève Almouzni) | Junior group leader | |||||
07/2000 | 04/2003 | Lyon, France | ENS Lyon, lab of Eric Gilson | Research Scientist | |||||
01/1997 | 06/2000 | Cambridge, USA | MIT, lab of Lenny Guarente | Postdoc | |||||
Education | |||||||||
Ecole Normale Supérieure, Paris, 1990-1993 PhD, Lille, 1996 HDR 2003 | |||||||||
报告内容：
DNA methylation is an essential epigenetic mark in mammals, and it needs to be maintained at each round of DNA replication. Two key actors in this epigenetic maintenance process are the DNA methyltransferase DNMT1, and an E3 ubiquitin ligase acting upstream of DNMT1, called UHRF1. How UHRF1 itself is recruited to replicating chromatin is incompletely understood. One of the mechanisms that was put forward is an interaction between the Tandem Tudor Domain (TTD) of UHRF1 and histone H3K9me2/3. Recently, we identified a new and unexpected mechanism that directly couples DNA replication and UHRF1 recruitment: a methylated histone-like region of DNA Ligase 1 (LIG1K126me2/me3) binds the UHRF1 TTD with nanomolar affinity, permitting UHRF1 recruitment to chromatin. We will report our recently obtained structure of the LIG1/UHRF1 complex, which sheds light on its regulation. We will also report on our unbiased CRISPR screen aimed at identifying new factors involved in DNA methylation maintenance.