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bioRxiv · 10.1101/523597

The KZFP/KAP1 system controls transposable elements-embedded regulatory sequences in adult T cells

Trono, D.·Marzetta, F.·Simo-Riudalbas, L.·Duc, J.·Planet, E.·Verp, S.·Turelli, P.
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Abstract

Transposable elements-embedded regulatory sequences (TEeRS) are subjected to early embryonic repression through sequence-specific recruitment of KRAB zinc finger proteins (KZFPs), their cofactor KAP1/TRIM28 and associated chromatin modifiers. This modulates the TEeRS-mediated regulation of gene expression in embryonic stem cells (ESCs) and leads to DNA methylation-induced silencing. However, KZFPs are broadly expressed in adult tissues, suggesting that they control TEeRS throughout life. Confirming this hypothesis, we reveal here that the KZFP/KAP1 system exerts a highly dynamic control of TEeRS in adult human CD4+ T lymphocytes. First, we observed that in these cells many TEs are still bound by KAP1, the recruitment of which is dynamically regulated upon T cell receptor stimulation. Second, we found that KAP1 depletion induces broad transcriptional alterations in T cells, with de-repression of TE-based regulatory elements leading to the illegitimate activation of nearby genes. Finally, we show that the tissue-restricted expression of KZFPs correlates with KAP1-mediated lineage-specific chromatin signatures and transcriptional repression. These data support a model where TE-targeting KZFPs and KAP1 are important regulators of gene expression in adult human cells.

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Trono, D., Marzetta, F., Simo-Riudalbas, L., Duc, J., Planet, E., Verp, S., Turelli, P.. 2019-01-19. The KZFP/KAP1 system controls transposable elements-embedded regulatory sequences in adult T cells. https://doi.org/10.1101/523597

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