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

Información del proyecto

TRANSPOS-X

Identificador del acuerdo de subvención: 694658

DOI

10.3030/694658

Proyecto cerrado

Fecha de la firma de la CE 13 Diciembre 2016

Fecha de inicio 1 Enero 2017

Fecha de finalización 31 Diciembre 2021

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 2 500 000,00

Aportación de la UE

€ 2 500 000,00

Coordinado por

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)

Período documentado: 2021-07-01 hasta 2021-12-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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