The Institute of Medical Science, The University Of Tokyo

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International Joint Usage/Research Center Seminar
"Genetic and structural investigations of DNA methylation maintenance mechanisms"

Seminar Date and Time: 12/02/2019 (Monday) 15:00 ~ 16:00
Venue: Building 1, 1F, Big Auditorium
Speaker (Name): Pierre-Antoine Defossez
Affiliation, Title: Epigenetics and Cell Fate, University Paris Diderot, Professor
Country: France
Subject: Genetic and structural investigations of DNA methylation maintenance mechanisms
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.
Language: English
Organizer (Host Researcher): Makoto Nakanishi