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bioRxiv · 10.1101/560391

Epigenetic inheritance of centromere identity in a heterologous system

Roure, V.·Medina-Pritchard, B.·Anselm, E.·Jeyaprakash, A. A.·Heun, P.
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Abstract

The centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, CENP-A, yet how its self-propagation is achieved remains poorly understood. Here we developed a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify the components required for dCENP-C loading onto chromatin, involving a cooperation between CAL1 and dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three Drosophila factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of centromere identity.

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Roure, V., Medina-Pritchard, B., Anselm, E., Jeyaprakash, A. A., Heun, P.. 2019-02-25. Epigenetic inheritance of centromere identity in a heterologous system. https://doi.org/10.1101/560391

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