Project description
Mobile DNA and gene activity
Transposable elements (TEs) are jumping genomic sequences that make up nearly half of the human and mouse genomes. Although most no longer move, many have been repurposed by cells as regulatory elements that control gene activity. These dual-purpose sequences can both support normal development and trigger harmful effects like cancer, making their regulation crucial. With the support of the Marie Skłodowska-Curie Actions programme, the TE-DRIVER project aims to understand how different TEs function as gene promoters and how their activity is influenced by their genomic surroundings. Researchers will investigate the role of chromatin, DNA methylation and genome structure overall on TE-drive transcription. Collectively, the study will provide fundamental knowledge on genome regulation.
Objective
"Transposable elements (TEs) make up about half of both the human and mouse genomes, playing a crucial role in genome plasticity and evolution. Most TEs have accumulated mutations that disable their transposition, but even fragmented TEs are often co-opted by the host into complex regulatory systems like promoters, enhancers and silencers, profoundly influencing gene and chromatin regulation. For example, a retrotransposon acts as a promoter to drive the expression of a specific isoform of Cdk2ap1, which is crucial for pre-implantation development. However, TEs can also trigger senescence and oncogene expression, making them a ""double-edged sword"" in biology. Given TEs’s dual role, the activity and regulation of TEs driving downstream transcription is extremely important for cellular homeostasis. Studies have suggested a potential role for TEs as promoters, yet evidence is fragmentary and indirect. The sufficiency of TEs in autonomously driving transcription, their interaction with genomic context, and differences between TEs in various genomic context remain largely unknown. The TE-Driver project aims to systematically and directly investigate TEs transcriptional activity and its regulation by genomic context such as DNA methylation, histone modifications and chromatin structure. TE-Driver will integrate representative TEs (MT2_Mm, L1MdTf_II, and B3A) into thousands of genomic locations in mouse embryonic stem cells (mESCs). TE integration sites will be captured via inverse PCR coupled with high-throughput sequencing, and transcriptome changes will be analyzed using Smart-seq+5’. The project will integrate these datasets with publicly available datasets on genomic context to evaluate TEs sufficiency in driving transcription within genomic contexts and elucidate differences among TEs. TE-Driver aims to advance our understanding of TE mechanisms in genome regulation and contribute to fields such as stem cell biology, developmental biology and functional genomics."
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
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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85764 Neuherberg
Germany
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