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ReaDMe SIGNED

Readout of DNA methylation

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EC-Contrib. €

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Project "ReaDMe" data sheet

The following table provides information about the project.

Coordinator
FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION 

Organization address
address: MAULBEERSTRASSE 66
city: BASEL
postcode: 4058
website: www.fmi.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˙136˙969 €
 EC max contribution 2˙136˙969 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION CH (BASEL) coordinator 2˙136˙969.00

Map

 Project objective

DNA and chromatin modifications are essential for proper control of gene expression during development. How these marks alter transcriptional programs and modulate binding patterns of sequence specific transcription factors (TF) remains poorly understood. This currently limits our interpretation of epigenomic maps towards their incorporation into predictive models of gene regulation. ReaDMe has the ambitious goal to systematically define the sensitivity of TFs to local levels of DNA methylation in vivo. We will use a combination of genomics, genome editing and proteomics tools to comprehensively identify transcriptional regulators that respond to DNA methylation. As a first approach, we will interrogate changes in the global TF binding landscape when DNA methylation is ablated from the genome. Using both embryonic stem cells and somatic cells, these experiments are aimed at identifying sites that are occupied by TFs in a DNA methylation dependent manner within different cellular context. Secondly, we will combine parallelized chromosomal insertions with targeted footprinting to determine the link between DNA sequence context, methylation density and TF binding. In a third approach we will define the global chromatin proteome as a function of DNA methylation. Through the use of a novel and orthogonal proteomics assay, we will characterize DNA methylation sensitive changes in the chromatin-bound proteome. Candidate factors predicted from all approaches will be validated and functionally characterized through direct genome-wide mapping as well as loss of function analysis. ERC funding would enable ReaDMe to develop an integrated setup to in vivo identify and characterize where DNA methylation influences the cis-regulatory landscape by modulating binding profiles of trans-acting factors. This goal represents a crucial step towards comprehensive understanding of the genomic readout of DNA methylation and its impact on gene regulation.

 Publications

year authors and title journal last update
List of publications.
2017 Dominik Hartl, Arnaud R. Krebs, Josephine Jüttner, Botond Roska, Dirk Schübeler
Cis-regulatory landscapes of four cell types of the retina
published pages: 11607-11621, ISSN: 0305-1048, DOI: 10.1093/nar/gkx923
Nucleic Acids Research 45/20 2019-07-02
2017 Colombo, Daniele F; Burger, Lukas; Baubec, Tuncay; Schübeler, Dirk
Binding of high mobility group A proteins to the mammalian genome occurs as a function of AT-content
published pages: , ISSN: 1553-7404, DOI: 10.5167/uzh-144792
PLoS Genetics 1 2019-07-02
2018 Paul Adrian Ginno, Lukas Burger, Jan Seebacher, Vytautas Iesmantavicius, Dirk Schübeler
Cell cycle-resolved chromatin proteomics reveals the extent of mitotic preservation of the genomic regulatory landscape
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06007-5
Nature Communications 9/1 2019-04-18

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