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REpiReg SIGNED

RNAi-mediated Epigenetic Gene Regulation

Total Cost €

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EC-Contrib. €

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Partnership

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 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.

critical    dissection    screens    mediated    trigger    proteomics    sparked    additional    mechanistic    synthetic    components    genetic    cell    link    unanswered    conserved    fragments    principles    organisms    trans    exogenously    eukaryotic    consists    sequencing    heterochromatin    systematic    rnas    builds    epigenetics    stem    impedes    counter    yeast    mutagenesis    mechanism    combined    expression    intriguing    novo    silence    refers    cutting    nucleases    mammalian    perform    chemical    rnai    homologous    surprising    rna    foundation    sirnas    small    single    close    mouse    initiation    de    endogenous    gene    epigenetic    gaps    employ    hampered    controversy    epigenome    experiments    difficult    elucidate    sequences    inherently    engineered    phenomenon    modifications    directed    chromatin    technologies    direct    genome    questions    regulation    fundamental    acting    possibility    fission    editing    cells    conservation    ago    beginning    edge    missing    fortunate    discovered    embryonic    outstanding    constitutes    decade    suppressive    regulatory   

Project "REpiReg" data sheet

The following table provides information about the project.

Coordinator
FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION 

Organization address
address: MAULBEERSTRASSE 66
city: BASEL
postcode: 4058
website: www.fmi.ch

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 https://buehlerlab.org/awards-honors/
 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

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION CH (BASEL) coordinator 1˙998˙557.00

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 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.

 Publications

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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