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PRCTOERC SIGNED

Novel Regulatory Principles of Polycomb Repressive Complex 2

Total Cost €

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EC-Contrib. €

0

Partnership

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 PRCTOERC project word cloud

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

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Project "PRCTOERC" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF EDINBURGH 

Organization address
address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL
website: www.ed.ac.uk

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˙496˙523 €
 EC max contribution 1˙496˙523 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) coordinator 1˙496˙523.00

Map

 Project objective

Posttranslational modifications of histone proteins have emerged as central regulators of gene expression. Through the factors that install, interpret, and erase them, histone marks control access to the genome, establishing chromatin environments that either support or counteract transcription. The histone methyltransferase Polycomb repressive complex 2 (PRC2) is crucially involved in gene repression all throughout development and adulthood, and it is often misregulated in cancer. Despite significant advances in the field, key aspects of PRC2 function remain largely elusive. The overarching goal of this project is to enhance our understanding of how PRC2 is regulated and how it controls the expression of developmental genes in embryonic stem cells. To this end, my research team and I will analyse how PRC2 cooperates with other histone modifiers and chromatin organisers at enhancers to achieve poising of developmental genes (Aim 1). These studies will enable us to appreciate how the pivotal PRC2 module interfaces with other players in the complex chromatin regulatory system, contributing to a much-needed integrated view of chromatin regulation. We will further unravel how generation of the recently discovered asymmetric nucleosomes, in which the two copies of histone H3 are disparately modified (Voigt et al., Cell, 2012), is controlled by PRC2-intrinsic catalytic properties and through interactions with other chromatin modifiers (Aim 2). This will ultimately allow modulating asymmetry in vivo, providing unprecedented means to assess its impact on PRC2 function and chromatin structure. Lastly, I aim to re-evaluate the issue of PRC2 recruitment to its target loci by employing a systems biology-informed quantitative approach (Aim 3). Together, the aims of this ambitious project will significantly advance our understanding of PRC2 and its role in the establishment of chromatin states, which are crucial to embryonic stem cell physiology and deregulated in cancer.

 Publications

year authors and title journal last update
List of publications.
2019 Konstantina Skourti-Stathaki, Elena Torlai Triglia, Marie Warburton, Philipp Voigt, Adrian Bird, Ana Pombo
R-Loops Enhance Polycomb Repression at a Subset of Developmental Regulator Genes
published pages: 930-945.e4, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.12.016
Molecular Cell 73/5 2020-02-04

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