Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS

Regulatory Logic, Thresholds and Epigenetic Memory: How cis-regulatory landscapes tune gene activity during mammalian development

Project description

Dissecting the regulation of gene expression during development

Multicellular organisms rely on a carefully regulated gene expression programme that drives cell differentiation and specification. The activity of developmental genes is tuned by cis-regulatory landscapes, but the precise mechanism remains elusive. The EU-funded CisTune project will focus on the X-inactive specific transcript (Xist) locus, which controls X-chromosome inactivation during development. The Xist seems to integrate sex- and developmental time-related signals to ensure transcription from only one chromosome in each cell. The project will unveil the regulatory principles that control the activity of the mammalian genome during development, offering important knowledge on the complexity of gene regulation.

Objective

Development of multicellular organisms relies on differential gene activation in a single genome. In response to multiple quantitative signals, cell-type specific transcriptional programs are established that determine cell identify. Their perturbation can result in pathologies such as cancer. Large cis-regulatory landscapes integrate information on cell state, space and time to precisely tune the activity of developmental genes. How cis-regulatory landscapes decode multiple quantitative signals remains poorly understood. CisTune aims at gaining a functional and mechanistic understanding of how regulator levels are sensed, how the input from multiple regulators is integrated and how information is processed by cis-regulatory landscapes.
CisTune will use the Xist locus as a model, which controls X-chromosome inactivation, an essential developmental process in mammals. Xist's cis-regulatory landscape integrates multiple quantitative input signals that transmit information on sex and developmental time, to ensure up-regulation from one X chromosome in each female cell. In CisTune we will thus study an essential process in great depth to identify regulatory principles that control activity of the mammalian genome during development.
CisTune will use an interdisciplinary approach at the intersection of systems biology, epigenetics and gene regulation, where highly multiplexed perturbation experiments of endogenous genes are interpreted with the help of mathematical models. We will build on recent technological breakthroughs, including single-cell genomics and high-throughput CRISPR screens, which we will complement with a new approach to functionally link sequence elements to their input signals. CisTune has the potential to overcome challenges that have prevented mammalian quantitative biology of gene regulation to becoming more broadly applied and will set the stage for investigating gene regulation across multiple layers of complexity.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

You need to log in or register to use this function

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-STG - Starting Grant

See all projects funded under this funding scheme

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2020-STG

See all projects funded under this call

Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 494 375,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

See on map

Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 494 375,00

Beneficiaries (1)

My booklet 0 0