DissectPcG SIGNED
Dissecting the Function of Multiple Polycomb Group Complexes in Establishing Transcriptional Identity
Total Cost €
0EC-Contrib. €
0Partnership
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Project "DissectPcG" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITA DEGLI STUDI DI MILANO
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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We will take advantage of newly developed reagents and unpublished genetic models to target each of the six Pcgf genes in either embryonic stem cells or mouse adult tissues.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 |
|---|---|---|---|
| 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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