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TransposonsReprogram SIGNED

How retrotransposons remodel the genome during early development and reprogramming

Total Cost €

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EC-Contrib. €

0

Partnership

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 TransposonsReprogram project word cloud

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

half    vitro    hypothesize    escs    orchestrate    circuits    finger    unknown    scenarios    gene    genes    understand    embryonic    esc    play    employed    data    differentiation    zfp819    sequences    bind    integrity    active    hypothesis    expressed    plasticity    reprogramming    genomes    fate    drive    regulate    serve    evolution    remodelled    zinc    co    assessing    crispr    viruses    mechanism    disruption    identification    dynamic    vivo    cell    zfps    questions    uncharacterized    enhancer    platforms    rtns    proteins    acting    ancient    occupy    implicated    neurons    longer    ours    dominate    promoter    genome    coevolved    human    therapies    reprogram    ask    structural    retrotransposons    transcription    retain    themselves    largely    shown    engaged    mobile    stably    mouse    repressor    stem    zfp37    contexts    cells    documented    recruit    opted    mammalian    function    developmental    cas9    unravel    broadly    remodel    genetic   

Project "TransposonsReprogram" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY COLLEGE LONDON 

Organization address
address: GOWER STREET
city: LONDON
postcode: WC1E 6BT
website: n.a.

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 United Kingdom [UK]
 Total cost 1˙499˙055 €
 EC max contribution 1˙499˙055 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2021-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON UK (LONDON) coordinator 1˙499˙055.00

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 Project objective

Retrotransposons (RTNs) are ancient viruses that have stably integrated themselves into mammalian genomes and they now occupy around half of the human or mouse genome. These mobile genetic elements that have coevolved with us drive evolution by creating new genes and plasticity of genomes. Exciting data including ours has shown that even RTNs that are no longer active retain enhancer, promoter or repressor sequences that regulate developmental genes, through largely uncharacterized transcription factors. We have employed CRISPR/Cas9 gene disruption to determine that Zfp37 and Zfp819 bind to and regulate RTNs in mouse embryonic stem cells (ESCs). Identification of these zinc finger proteins (ZFPs) now allows us to ask new questions about how RTNs have been co-opted to orchestrate gene circuits in vitro and in vivo. Both these factors have already been implicated to play a role in reprogramming or genome integrity.

We hypothesize that RTNs have been co-opted to remodel the genome by acting as structural platforms that recruit transcription factors like Zfp37 and Zfp819. We will test this hypothesis assessing the role of RTNs and these two ZFPs in three dynamic contexts where the genome is remodelled. These are in ESC differentiation to neurons, in reprogramming and in early mouse development, three scenarios where RTNs have been documented to become expressed and serve an unknown function.

This work will exploit mouse development to unravel the mechanism of how RTNs remodel the genome. It will help us to understand how ZFPs can be engaged to reprogram cells and in stem-cell therapies, and will explain more broadly how RTNs, which dominate our genomes, control cell fate.

 Publications

year authors and title journal last update
List of publications.
2017 Luisa Robbez-Masson, Christopher H.C. Tie, Helen M. Rowe
Cancer cells, on your histone marks, get SETDB1, silence retrotransposons, and go!
published pages: 3429-3431, ISSN: 0021-9525, DOI: 10.1083/jcb.201710068
The Journal of Cell Biology 216/11 2019-08-29
2018 Christopher HC Tie, Liane Fernandes, Lucia Conde, Luisa Robbez‐Masson, Rebecca P Sumner, Tom Peacock, Maria Teresa Rodriguez‐Plata, Greta Mickute, Robert Gifford, Greg J Towers, Javier Herrero, Helen M Rowe
KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control
published pages: e45000, ISSN: 1469-221X, DOI: 10.15252/embr.201745000
EMBO reports 19/10 2019-08-30

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