Objective
Enhancers are genomic domains that regulate transcription of distantly located genes and that are characterized by specific chromatin signatures of histone methylation and acetylation patterns. Interestingly, RNA polymerase II (RNAPII) binds to a subset of enhancers and produces transcripts, called enhancer RNAs (eRNAs). These are produced bi-directionally and, in contrast to mRNAs and many other non-coding RNAs, are not polyadenylated. Generally, the transcription of eRNAs was shown to positively correlate with mRNA levels of surrounding protein-coding genes. However, it is unclear if eRNAs carry a transcriptional function.
p53 is a transcription factor and tumor suppressor that is very frequently mutated in cancer. Chromatin-binding profiles reveal specific interactions of p53 with promoter regions of nearby genes, within genes, but also with remote regions located more than 50 kbps away from any known gene. Interestingly, many of these remote regions possess evolutionary highly conserved p53-binding sites and all known hallmarks of enhancer regions, as well as binding of RNAPII. We found out that many remote p53-bound domains are indeed p53-dependent eRNA-producing enhancers, and, most importantly, eRNA production was required for transcriptional induction of distal genes and for p53-dependent cellular control.
Here we will:
1. Investigate in detail the mechanism of action and function of p53-dependent eRNAs.
2. Expand studies to identify eRNAs with oncogenic function.
3. Develop efficient ways to target eRNAs.
4. Target eRNAs and study their capacity to inhibit tumorigenicity.
As eRNAs are mediators of enhancer activity with sequence specific content and sensitivity to siRNA targeting, they might be the Achilles heel through which oncogenic enhancer activity could be suppressed. Our study will elucidate a novel layer of gene regulation and holds promise for opening up new opportunities to affect cancer-related cellular programs in very specific and effectiv
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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.
ERC-2012-ADG_20120314
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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.
Host institution
1066 CX AMSTERDAM
Netherlands
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.