Event date:
Aug 27 2020 1:00 pm

How and where to assemble heterochromatin, and why it is essential for organismal survival

Speaker(s)
Professor Susan Gasser
Venue
Zoom/Online
Abstract
The establishment and maintenance of chromatin domains shape the epigenetic memory of a cell, with histone H3 lysine 9 methylation (H3K9me) defining repressed heterochromatin. In C. elegans, SET-25 (SUV39/G9a) catalyzes H3K9me1-3, while MET-2 (SetDB1) mediates H3K9me1-2. We define here two distinct pathways that recruit SET-25 to its targets. One requires recognition of MET-2-mediated H3K9me2 by the MBT-domain protein LIN-61. The second depends on a somatic Argonaut NRDE-3 and 22nt siRNAs. This MET-2-independent pathway makes up ~10% of SET-25 target sequences, and most notably includes intact transposons. Compared to single mutants, met-2;nrde-3 double mutant enhances transposon transcription and embryonic lethality. Whereas the targeting of SET-25 silences transposons, whose expression compromises development, the targeting of MET-2/SET-DB1 is necessary to prevent the promiscuous transcription of simple repeats. Simple repeat transcripts lead to R-loops and fork associated damage, that requires BRCA1 to ensure survival. While the genome becomes unstable, met-2 mutants show nearly normal developmental and differentiation patterns.

Prof. Dr. Susan Gasser gave a talk in our Colloquium “zooming Molecular & Cellular Biology” series. Prof. Gasser is a highly accomplished scientist who has contributed significantly to the fields of DNA replication, DNA damage repair and gene regulation. Having served FMI Switzerland for fourteen years as Director, Prof. Gasser is a member of the ETH Board, the Swiss Science Council, and sits on the scientific advisory board of the Helmholtz institutes of Germany, the Max Planck Institute for Biophysical chemistry, the Francis Crick Institute in London and the European Molecular Biology Laboratory (EMBL) in Heidelberg. At the Swiss National Science Foundation (SNF) she chaired the Equality Commission from 2014 to the end of 2019.

Susan Gasser studied biology and biophysics at the University of Chicago and received her doctorate in biochemistry from the University of Basel. From 1986 she was group leader at the Swiss Institute for Experimental Cancer Research (ISREC) in Lausanne until 2001, when she was appointed full professor at the University of Geneva. From November 2004 until March 2019 she was Director of the Friedrich Miescher Institute for Biomedical Research (FMI), where she still heads her research group. Since 2005 she has also been a full professor for molecular biology at the University of Basel. Gasser is a member of the ETH Board, the Swiss Science Council, and sits on the scientific advisory board of the Helmholtz institutes of Germany, the Max Planck Institute for Biophysical chemistry, the Francis Crick Institute in London and the European Molecular Biology Laboratory (EMBL) in Heidelberg. At the Swiss National Science Foundation (SNF) she chaired the Equality Commission from 2014 to the end of 2019.