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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.

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   advantage    repressive    manner    function    reagents    tissues    differentiation    27    variety    unpublished    systematically    prc1    relative    methylation    ubiquitination    pcgs    heterogeneity    regulating    mutually    co    functions    molecular   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

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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