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Enhancer ID SIGNED

Identification and functional characterization of mammalian enhancers and transcriptional co-factors during cellular signaling and cell fate transitions

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EC-Contrib. €

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Project "Enhancer ID" data sheet

The following table provides information about the project.

Coordinator
FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH 

Organization address
address: CAMPUS-VIENNA-BIOCENTER 1
city: WIEN
postcode: 1030
website: www.imp.ac.at

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 Austria [AT]
 Project website https://www.imp.ac.at/research/research-groups/alexander-stark/research/
 Total cost 1˙999˙906 €
 EC max contribution 1˙999˙906 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2021-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH AT (WIEN) coordinator 1˙999˙906.00

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 Project objective

A major goal in biology is to understand how gene regulatory information is encoded by the human genome and how it defines different gene expression programs and cell types. Enhancers are genomic elements that control transcription, yet despite their importance, only a minority of enhancers are known and functionally characterized. In particular, their activity changes during cellular signalling or cell type transitions are largely elusive. Furthermore, fundamental questions about transcriptional co-factors have remained unanswered even though they regulate enhancer activities and have become attractive therapeutic targets, e.g. for cancer treatment.

Here, I propose a functional genomics approach in mammalian cells with three specific objectives: First, we will identify and functionally characterize transcriptional enhancers in selected human and mouse cells using the recently developed quantitative enhancer activity assay STARR-seq. Second, we will determine enhancer activity changes quantitatively during steroid hormone signalling, cell differentiation, and malignant transformation to reveal enhancers that are important for these processes. Third, we will systematically dissect the functional relationship of enhancers and transcriptional co-factors.

This proposal uses emerging in-house technology to address fundamental questions in enhancer biology and complement the genome-wide profiling of gene expression and chromatin states (e.g. by ENCODE). We will gain insights into the genomic organization of active enhancers and reveal chromatin or sequence features associated with dynamic activity changes. I also expect that we will be able to define co-factor requirements for enhancer function and reveal if different types of enhancers exist. Given our expertise in experimental and computational approaches and STARR-seq, I anticipate that we reach our aims and make major contributions to the understanding of gene regulation in mammals.

 Publications

year authors and title journal last update
List of publications.
2018 Felix Muerdter, Łukasz M Boryń, Ashley R Woodfin, Christoph Neumayr, Martina Rath, Muhammad A Zabidi, Michaela Pagani, Vanja Haberle, Tomáš Kazmar, Rui R Catarino, Katharina Schernhuber, Cosmas D Arnold, Alexander Stark
Resolving systematic errors in widely used enhancer activity assays in human cells
published pages: 141-149, ISSN: 1548-7091, DOI: 10.1038/nmeth.4534
Nature Methods 15/2 2020-03-17
2017 Alexandra Franz, Daria Shlyueva, Erich Brunner, Alexander Stark, Konrad Basler
Probing the canonicity of the Wnt/Wingless signaling pathway
published pages: e1006700, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006700
PLOS Genetics 13/4 2020-03-17
2018 Rui R. Catarino, Alexander Stark
Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation
published pages: 202-223, ISSN: 0890-9369, DOI: 10.1101/gad.310367.117
Genes & Development 32/3-4 2020-03-17

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