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

Periodic Reporting for period 3 - TRANSPOS-X (Transposable elements, their controllers and the genesis of human-specific transcriptional networks)

Reporting period: 2020-01-01 to 2021-06-30

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.
Our work so far 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, and 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. We have also uncovered TE-based biomarkers of great potentiall value for precision oncology.
We hope to decipher how KZFPs and TEs regulate genome expression and thus exert a profound influence on human development and biology, notably shaping the human brain, a hallmark of our speciation. We also anticipate to generate a large collection of TE-based biomarkers with great diagnostic, prognostic and theranostic value in the management of cancer.