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RNAi-mediated Epigenetic Gene Regulation

Total Cost €


EC-Contrib. €






 REpiReg project word cloud

Explore the words cloud of the REpiReg project. It provides you a very rough idea of what is the project "REpiReg" about.

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Project "REpiReg" data sheet

The following table provides information about the project.


Organization address
city: BASEL
postcode: 4058

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Project website
 Total cost 1˙998˙557 €
 EC max contribution 1˙998˙557 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

RNAi refers to the ability of small RNAs to silence expression of homologous sequences. A surprising link between epigenetics and RNAi was discovered more than a decade ago, and I was fortunate enough to be involved in this exciting field of research from the beginning. It is now well established that endogenous small RNAs have a direct impact on the genome in various organisms. Yet, the initiation of chromatin modifications in trans by exogenously introduced small RNAs has been inherently difficult to achieve in all eukaryotic cells. This has sparked controversy about the importance and conservation of RNAi-mediated epigenome regulation and hampered systematic mechanistic dissection of this phenomenon. Using fission yeast, we have discovered a counter-acting mechanism that impedes small RNA-directed formation of heterochromatin and constitutes the foundation of this proposal. Our goal is to close several knowledge gaps and test the intriguing possibility that the suppressive mechanism we discovered is conserved in mammalian cells. We will employ yeast and embryonic stem cells and use cutting-edge technologies (i.e., chemical mutagenesis combined with whole-genome sequencing, genome editing with engineered nucleases, and single-cell RNA sequencing) to address fundamental, as yet unanswered questions. My proposal consists of four major aims. In aim 1, I propose to use proteomics approaches and to perform yeast genetic screens to define additional pathway components and regulatory factors. Aim 2 builds on our ability to finally trigger de novo formation of heterochromatin by synthetic siRNAs acting in trans, addressing many of the outstanding mechanistic questions that could not be addressed in the past. In Aims 3 and 4, experiments conducted in yeast and mouse cells will elucidate missing fragments critical to our understanding of the conserved principles behind RNAi-mediated epigenetic gene regulation.


year authors and title journal last update
List of publications.
2016 Yukiko Shimada, Fabio Mohn, Marc Bühler
The RNA-induced transcriptional silencing complex targets chromatin exclusively via interacting with nascent transcripts
published pages: 2571-2580, ISSN: 0890-9369, DOI: 10.1101/gad.292599.116
Genes & Development 30/23 2019-06-18
2017 Valentin Flury, Paula Raluca Georgescu, Vytautas Iesmantavicius, Yukiko Shimada, Tahsin Kuzdere, Sigurd Braun, Marc B?hler
The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.05.026
Molecular Cell 2019-06-18
2019 Lea Duempelmann, Fabio Mohn, Yukiko Shimada, Daniele Oberti, Aude Andriollo, Silke Lochs, Marc Bühler
Inheritance of a Phenotypically Neutral Epimutation Evokes Gene Silencing in Later Generations
published pages: 534-541.e4, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.02.009
Molecular Cell 74/3 2019-08-30

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