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ReaDMe SIGNED

Readout of DNA methylation

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

ReaDMe project word cloud

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

occupied programs link predictive models candidate function regulatory poorly patterns chromatin validated global acting regulators sites modulate direct proteome genomics local combine cellular functionally transcription influences sensitive genomic manner stem proteomics cis footprinting mapping dependent transcriptional profiles tools epigenomic modulating erc dna setup secondly genome sensitivity interpretation readout alter editing regulation systematically sequence assay context parallelized readme combination interrogate vivo limits density orthogonal modifications levels methylation experiments expression landscape gene maps first chromosomal proper tf predicted incorporation ablated embryonic somatic insertions bound trans binding cells marks comprehensively tfs

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 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.	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

List of publications.
year	authors and title	journal	last update
2017	Dominik Hartl, Arnaud R. Krebs, Josephine JÃ¼ttner, Botond Roska, Dirk SchÃ¼beler 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; SchÃ¼beler, 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 SchÃ¼beler 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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