Objective
In multicellular organisms, during embryogenesis and tissue homeostasis the differentiation of pluripotent stem cells into a variety of specialized cell types is governed by diverse transcriptional programs, the establishment and maintenance of which rely on epigenetic mechanisms, such as chromatin modifications. Over the past years, a large number of post-translational modifications of histones as well as enzymes responsible for either positioning or removal of these marks were characterized. Genome-wide studies mapping the distribution of histone modifications revealed a complex epigenetic landscape on eukaryotic chromosomes. In particular, distinct chromatin signatures were recently associated with enhancer elements, cis-acting DNA sequences inducing transcription from target promoters. However, whether the deposition of specific marks at enhancers is a pre-requisite for their activity or a mere consequence of the recruitment of histone-modifying complexes at their target promoters is an entirely open question.
The aim of this proposal is to define the biological significance of histone modifications covering enhancer sequences in vivo. To perform this study we will generate transgenic mice allowing us to target histone-modifying activities at enhancers using a recently introduced technology based on transcription activator–like effectors (TALEs). The developing limb will serve as a model system since several well-defined enhancers are active specifically in this structure. We will validate this approach by assessing changes in histone marks over enhancer sequences in transgenic versus wild type mice. Next, we will determine how such changes affect the transcriptional status of the endogenous target gene of the enhancer by scoring both RNA levels and limb phenotypes. The results of this study are likely to have a major impact on our understanding of chromatin functions in transcriptional regulation.
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.
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.
- natural sciences biological sciences developmental biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics chromosomes
- medical and health sciences basic medicine physiology homeostasis
- natural sciences biological sciences genetics genomes eukaryotic genomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-CIG
See other projects for this call
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.
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
55128 Mainz
Germany
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.