Transposable elements, their controllers and the genesis of human-specific transcriptional networks

Informazioni relative al progetto

TRANSPOS-X

ID dell’accordo di sovvenzione: 694658

DOI

10.3030/694658

Progetto chiuso

Data della firma CE 13 Dicembre 2016

Data di avvio 1 Gennaio 2017

Data di completamento 31 Dicembre 2021

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 500 000,00

Contributo UE

€ 2 500 000,00

Coordinato da

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland

Periodic Reporting for period 4 - TRANSPOS-X (Transposable elements, their controllers and the genesis of human-specific transcriptional networks)

Periodo di rendicontazione: 2021-07-01 al 2021-12-31

Sintesi del contesto e degli obiettivi generali del progetto

This projects explores how the genome regulatory power of transposable elements (TEs), which contribute more than half of our DNA, and of their KRAB-containing zinc finger protein (KZFP) controllers shape human speciation, development and physiology, how alterations of this system can lead to pathologies, and how the resulting knowledge can be exploited in medicine, for instance to fight cancer.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Our work has yielded an important sum of novel information on how some 350 human KZFPs recognize their TE targets, how these KZFPs functionally diversified throughout evolution, how they act during early embryogenesis to tame the regulatory power of TEs in order to facilitate its domestication for the benefit of the host, and how TEs and their KZFP controllers have fed higher vertebrates with cis- and trans-acting regulatory sequences that likely influence all aspects of human biology. Turning to the involvement of this system in human pathologies, we have discovered TE-based biomarkers of great potential value for precision oncology, and unveiled how the the genomic surveillance exerted by KZFPs is perverted in the context of cancer cells, where it confers protection against the genotoxic consequences of pro-oncogenic epigenetic changes. These results reveal an important role for a family of largely species-restricted proteins in the pathogenesis of human cancer, and also point to new avenues for therapeutic intervention.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Our achievements shed an important light on what has so far been a black box of human biology, revealing intricate roles for TEs and their KZFP controllers in human speciation, development, physiology and disease susceptibility.

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