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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.

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

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

Map

 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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