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METACHROM SIGNED

Establishment and maintenance of gene expression by heterochromatin factors

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 METACHROM project word cloud

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

establishment    tethering    methyl    maintenance    environmental    life    stem    setdb1    imparts    lysine    instruct    tri    adult    obtain    transferase    diseases    chromatin    epialleles    maintained    retrovirus    epigenome    epigenetic    stress    adapt    heterochromatin    nearby    regulated    map    deepen    environment    locus    variably    variegation    identical    methylating    influenced    hypothesize    embryonic    telomeric    alleles    repression    insertion    transcription    positions    silenced    surprisingly    model    h3k9me3    understand    epiallele    transcriptional    mescs    mammals    picture    individuals    mechanisms    genetically    metastable    shape    proteomics    expressed    first    endogenous    mouse    active    correlates    critical    histone    found    contexts    h3    induces    either    effect    subsequently    modifications    stimuli    enhanced    aging    dependent    expression    installed    silencing    gene    genome    position    reconstituted    underlying    regulation    telomeres    genes    cells   

Project "METACHROM" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

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 France [FR]
 Total cost 1˙999˙025 €
 EC max contribution 1˙999˙025 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙999˙025.00

Map

 Project objective

Metastable epialleles are alleles that are variably expressed in genetically identical individuals. These epialleles are established during early development by epigenetic modifications in a process influenced by stress and the environment. The epiallele’s state can subsequently be maintained throughout development and adult life. Studying the mechanisms underlying establishment and maintenance of chromatin states is critical to understanding how the environment can shape the epigenome and how it can impact on diseases and aging. Most mouse metastable epialleles result from a nearby insertion of an endogenous retrovirus, which induces position effect variegation. In mouse embryonic stem cells, these elements are silenced by the histone methyl-transferase SETDB1 which imparts heterochromatin features by tri-methylating histone H3 on lysine 9. In the same cells, telomeric H3K9me3 is also installed by SETDB1 but surprisingly, we found that H3K9me3 correlates with enhanced transcriptional activity at telomeres. I hypothesize here that metastable chromatin states are controlled by H3K9me3 and associated factors, which are targeted to defined positions that can either instruct silencing, or support active expression. To understand how metastable chromatin states are regulated, we will first use a locus-specific chromatin proteomics approach to identify H3K9me3-dependent factors in the contexts of transcription or repression. Next, both pathways will be reconstituted by tethering those factors at specific positions on model genes, and maintenance of these states will be analyzed. Finally, to obtain a comprehensive picture of the metastable states establishment and maintenance, we will map heterochromatin factors genome-wide, in response to distinct stimuli in mESCs. This proposal will deepen our understanding of the mechanisms by which mammals use gene regulation to adapt to environmental conditions.

 Publications

year authors and title journal last update
List of publications.
2019 Mathilde Gauchier, Sophie Kan, Amandine Barral, Sandrine Sauzet, Eneritz Agirre, Erin Bonnell, Nehmé Saksouk, Teresa K. Barth, Satoru Ide, Serge Urbach, Raymund J. Wellinger, Reini F. Luco, Axel Imhof, Jérôme Déjardin
SETDB1-dependent heterochromatin stimulates alternative lengthening of telomeres
published pages: eaav3673, ISSN: 2375-2548, DOI: 10.1126/sciadv.aav3673
Science Advances 5/5 2020-02-06
2019 Sofie Traynor, Niels Erik Møllegaard, Mikkel G Jørgensen, Nadine H Brückmann, Christina B Pedersen, Mikkel G Terp, Simone Johansen, Jerome Dejardin, Henrik J Ditzel, Morten F Gjerstorff
Remodeling and destabilization of chromosome 1 pericentromeric heterochromatin by SSX proteins
published pages: 6668-6684, ISSN: 0305-1048, DOI: 10.1093/nar/gkz396
Nucleic Acids Research 47/13 2020-02-06
2019 Camille Dion, Stéphane Roche, Camille Laberthonnière, Natacha Broucqsault, Virginie Mariot, Shifeng Xue, Alexandra D Gurzau, Agnieszka Nowak, Christopher T Gordon, Marie-Cécile Gaillard, Claire El-Yazidi, Morgane Thomas, Andrée Schlupp-Robaglia, Chantal Missirian, Valérie Malan, Liham Ratbi, Abdelaziz Sefiani, Bernd Wollnik, Bernard Binetruy, Emmanuelle Salort Campana, Shahram Attarian, Rafa
SMCHD1 is involved in de novo methylation of the DUX4 -encoding D4Z4 macrosatellite
published pages: 2822-2839, ISSN: 0305-1048, DOI: 10.1093/nar/gkz005
Nucleic Acids Research 47/6 2020-02-06
2018 Mathieu Tardat, Jérôme Déjardin
Telomere chromatin establishment and its maintenance during mammalian development
published pages: 3-18, ISSN: 0009-5915, DOI: 10.1007/s00412-017-0656-3
Chromosoma 127/1 2019-06-11

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