Objective
Epigenetic silencing is essential for modulating gene expression patterns in developing organisms and has very big impact on the genome integrity. Cancer, as well as many other diseases, has been linked to the changes in transcription of regulatory genes due to the aberrant epigenetic silencing. Despite many epigenetic regulators, enzymes including histone deacetylases, methyltransferases, and DNA methyltransferases, were discovered, it is critical to bridge the gap in our understanding of the mechanisms contributing to chromatin structure modulation. We employed a phenotypic screening assay in mouse erythroid leukemia cells that harbour a silenced green fluorescent protein (GFP) reporter transgene in order to isolate new components of heterochromatic silencing and identify compounds that have potential to de-repress tumour suppressor genes in cancer cells. Strikingly among the compounds with strong anti-silencing properties we found inhibitors of bromo and extra-terminal domain (BET) proteins, which recently became massively popular as new generation chemotherapy anti-cancer drugs. Since so far BET proteins were mainly considered to act as transcriptional co-activators, we have set out to investigate the molecular mechanism of action of the BET inhibitors with respect to their anti-silencing properties. Our preliminary data suggests that inhibition of BET proteins results in loss of the DNA methylation, and specific histone modifications from heterochromatic regions. The aims of this proposal are: 1) To determine which BET proteins are important for heterochromatin maintenance; 2) To determine the mechanism of action of the key BET protein(s) in epigenetic silencing; 3) To analyse chromatin changes resulting from inhibiting of the key BET protein(s) in the selected cancer cell lines. We expect that this research will not only shed light on fundamental principles of genome organization, but also will instruct cancer research and lead to new therapeutic approaches.
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 genetics DNA
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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-2013-IEF
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.
Coordinator
EH8 9YL Edinburgh
United Kingdom
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.