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DissectPcG SIGNED

Dissecting the Function of Multiple Polycomb Group Complexes in Establishing Transcriptional Identity

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EC-Contrib. €

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 DissectPcG project word cloud

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

tri    biological    ubiquitination    mutually    pcgf    elucidate    genes    share    core    variety    repressive    cell    deregulation    unclear    modifiers    methylation    pcg    systematically    regulating    dissects    biochemical    establishment    119    subunits    gene    advantage    programs    expression    heterogeneous    pcgs    differ    tissue    composition    maintenance    forms    pcgf1    published    mechanistic    contribution    newly    transcriptional    cellular    prc1    unpublished    phenotypes    catalyses    group    27    h3    tumours    prc2    complexes    largely    six    mutations    histone    mouse    contributions    classified    reagents    line    their    dissect    models    fundamental    lysine    catalytic    mechanisms    profiles    tissues    molecular    co    embryonic    cancer    cells    altered    retains    subunit    function    exclusive    differentiation    exist    polycomb    chromatin    gain    genetic    h2a    critically    links    functions    assembling    correct    either    stem    adult    manner    relative    unknown    heterogeneity    underlying    identity    homeostasis    renewal    self   

Project "DissectPcG" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI MILANO 

Organization address
address: Via Festa Del Perdono 7
city: MILANO
postcode: 20122
website: www.unimi.it

contact info
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surname: n.a.
function: n.a.
email: n.a.
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fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (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 2017-11-01   to  2022-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI MILANO IT (MILANO) coordinator 829˙932.00
2    ISTITUTO EUROPEO DI ONCOLOGIA SRL IT (MILANO) participant 1˙170˙067.00

Map

 Project objective

The activities of the Polycomb group (PcG) of repressive chromatin modifiers are required to maintain correct transcriptional identity during development and differentiation. These activities are altered in a variety of tumours by gain- or loss-of-function mutations, whose mechanistic aspects still remain unclear.

PcGs can be classified in two major repressive complexes (PRC1 and PRC2) with common pathways but distinct biochemical activities. PRC1 catalyses histone H2A ubiquitination of lysine 119, and PRC2 tri-methylation of histone H3 lysine 27. However, PRC1 has a more heterogeneous composition than PRC2, with six mutually exclusive PCGF subunits (PCGF1–6) essential for assembling distinct PRC1 complexes that differ in subunit composition but share the same catalytic core.

While up to six different PRC1 forms can co-exist in a given cell, the molecular mechanisms regulating their activities and their relative contributions to general PRC1 function in any tissue/cell type remain largely unknown. In line with this biochemical heterogeneity, PRC1 retains broader biological functions than PRC2. Critically, however, no molecular analysis has yet been published that dissects the contribution of each PRC1 complex in regulating transcriptional identity.

We will take advantage of newly developed reagents and unpublished genetic models to target each of the six Pcgf genes in either embryonic stem cells or mouse adult tissues. This will systematically dissect the contributions of the different PRC1 complexes to chromatin profiles, gene expression programs, and cellular phenotypes during stem cell self-renewal, differentiation and adult tissue homeostasis. Overall, this will elucidate some of the fundamental mechanisms underlying the establishment and maintenance of cellular identity and will allow us to further determine the molecular links between PcG deregulation and cancer development in a tissue- and/or cell type–specific manner.

 Publications

year authors and title journal last update
List of publications.
2019 Elisa Lavarone, Caterina M. Barbieri, Diego Pasini
Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09624-w
Nature Communications 10/1 2019-06-27
2019 Silvia Pivetti, Daniel Fernandez-Perez, Alessandro D’Ambrosio, Caterina Maria Barbieri, Daria Manganaro, Alessandra Rossi, Laura Barnabei, Marika Zanotti, Andrea Scelfo, Fulvio Chiacchiera, Diego Pasini
Loss of PRC1 activity in different stem cell compartments activates a common transcriptional program with cell type–dependent outcomes
published pages: eaav1594, ISSN: 2375-2548, DOI: 10.1126/sciadv.aav1594
Science Advances 5/5 2019-08-05
2019 Andrea Scelfo, Daniel Fernández-Pérez, Simone Tamburri, Marika Zanotti, Elisa Lavarone, Monica Soldi, Tiziana Bonaldi, Karin Johanna Ferrari, Diego Pasini
Functional Landscape of PCGF Proteins Reveals Both RING1A/B-Dependent-and RING1A/B-Independent-Specific Activities
published pages: 1037-1052.e7, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.04.002
Molecular Cell 74/5 2019-06-27

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