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RegulHox SIGNED

Topological organization of vertebrate regulatory landscapes: The Hox genes paradigm

Total Cost €

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EC-Contrib. €

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Partnership

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 RegulHox project word cloud

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

matching    genes    normal    they    preliminary    engineered    mutations    tissues    associating    suggest    embryos    mice    topological    think    embryonic    chromosomes    usually    initiated    2q31    cultures    series    covered    associate    cutting    allelic    realized    regulations    edge    grant    dna    context    originality    pilot    technological    topologically    impaired    developmental    interdisciplinary    novelty    genomic    locus    human    genetically    hoxd    regulatory    containing    genetic    bases    re    variations    technologies    adult    evolution    chromosome    topology    tads    feasibility    collection    generally    cell    delay    cluster    enhancer    chromatin    modalities    syndromes    paradigm    interval    emerged    discrete    cnvs    tools    understand    physiological    pleiotropic    hic    mechanistic    domains    arrangements    kept    believe    portfolio    topologies    capitalize    syntenic    organizing    vivo    partitions    experiments    laboratory    living    mammalian    functions    mouse    experimental   

Project "RegulHox" data sheet

The following table provides information about the project.

Coordinator
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE 

Organization address
address: BATIMENT CE 3316 STATION 1
city: LAUSANNE
postcode: 1015
website: www.epfl.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]
 Total cost 2˙499˙628 €
 EC max contribution 2˙499˙628 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE CH (LAUSANNE) coordinator 2˙499˙628.00

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 Project objective

The aim of this grant is to understand how mammalian developmental genes, which are usually pleiotropic, are controlled via long-range regulations and how chromatin partitions into large and discrete regulatory domains, generally matching Topologically Associating Domains (TADs). We want to understand how such domains emerged in evolution, how they are built during development and how they help implement enhancer functions. We will use a large genomic interval in mouse chromosome 2 containing the HoxD cluster as a paradigm, as it is covered by a large allelic series re-organizing the topology of this interval. Since the syntenic human locus (2q31) is affected in numerous genetic syndromes involving CNVs or large DNA re-arrangements, we believe this work will also help understand the mechanistic bases of human regulatory mutations. The approach will capitalize on our knowledge of mouse embryos, the implementation of cutting-edge genomic technologies and the unique collection of engineered mammalian chromosomes kept into living mice, which represent as many targeted re-organizations of both chromatin and regulatory topologies. It will require important technological development, in order to apply to mammalian embryos, methods (HiC) currently used for cell cultures or adult tissues. We think that the feasibility of this novel program is high, due the portfolio of experimental tools recently developed in our laboratory. Also, pilot experiments have been initiated to identify problems and preliminary results including the use of HiC on embryonic tissues suggest that the proposed experiments can be realized within delay. The novelty and originality of this program are in the interdisciplinary and system approach of genomic re-arrangements, as analyzed in vivo using recently developed methodologies, allowing to associate topological variations with regulatory modalities in a physiological context, during normal or genetically impaired embryonic development.

 Publications

year authors and title journal last update
List of publications.
2016 Isabel Guerreiro, Sandra Gitto, Ana Novoa, Julien Codourey, Thi Hanh Nguyen Huynh, Federico Gonzalez, Michel C Milinkovitch, Moises Mallo, Denis Duboule
Reorganisation of Hoxd regulatory landscapes during the evolution of a snake-like body plan
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.16087
eLife 5 2019-07-02
2016 Ruben Schep, Anamaria Necsulea, Eddie Rodríguez-Carballo, Isabel Guerreiro, Guillaume Andrey, Thi Hanh Nguyen Huynh, Virginie Marcet, Jozsef Zákány, Denis Duboule, Leonardo Beccari
Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape
published pages: E7720-E7729, ISSN: 0027-8424, DOI: 10.1073/pnas.1617141113
Proceedings of the National Academy of Sciences 113/48 2019-07-02
2017 Eddie Rodríguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre J. Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hanh Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule
The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes
published pages: 2264-2281, ISSN: 0890-9369, DOI: 10.1101/gad.307769.117
Genes & Development 31/22 2019-07-02
2017 Pierre J. Fabre, Marion Leleu, Benjamin H. Mormann, Lucille Lopez-Delisle, Daan Noordermeer, Leonardo Beccari, Denis Duboule
Large scale genomic reorganization of topological domains at the HoxD locus
published pages: , ISSN: 1474-760X, DOI: 10.1186/s13059-017-1278-z
Genome Biology 18/1 2019-07-02
2016 Leonardo Beccari, Nayuta Yakushiji-Kaminatsui, Joost M. Woltering, Anamaria Necsulea, Nicolas Lonfat, Eddie Rodríguez-Carballo, Benedicte Mascrez, Shiori Yamamoto, Atsushi Kuroiwa, Denis Duboule
A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus
published pages: , ISSN: 0890-9369, DOI: 10.1101/gad.281055.116
Genes & Development 2019-07-02
2017 Jozsef Zakany, Fabrice Darbellay, Bénédicte Mascrez, Anamaria Necsulea, Denis Duboule
Control of growth and gut maturation by HoxD genes and the associated lncRNA Haglr
published pages: E9290-E9299, ISSN: 0027-8424, DOI: 10.1073/pnas.1712511114
Proceedings of the National Academy of Sciences 114/44 2019-07-02
2015 Pierre J. Fabre, Alexander Benke, Elisabeth Joye, Thi Hanh Nguyen Huynh, Suliana Manley, Denis Duboule
Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states
published pages: 13964-13969, ISSN: 0027-8424, DOI: 10.1073/pnas.1517972112
Proceedings of the National Academy of Sciences 112/45 2019-07-02
2017 Alan R. Rodrigues, Nayuta Yakushiji-Kaminatsui, Yuji Atsuta, Guillaume Andrey, Patrick Schorderet, Denis Duboule, Clifford J. Tabin
Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells
published pages: 3139-3144, ISSN: 0027-8424, DOI: 10.1073/pnas.1620767114
Proceedings of the National Academy of Sciences 114/12 2019-07-02
2016 Ana Rita Amândio, Anamaria Necsulea, Elisabeth Joye, Bénédicte Mascrez, Denis Duboule
Hotair Is Dispensible for Mouse Development
published pages: e1006232, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006232
PLOS Genetics 12/12 2019-07-02
2017 Jacqueline Deschamps, Denis Duboule
Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock
published pages: 1406-1416, ISSN: 0890-9369, DOI: 10.1101/gad.303123.117
Genes & Development 31/14 2019-07-02

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