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bioRxiv · 10.64898/2026.07.16.738894

Co-option of CENP-A for activity-induced neuronal plasticity

Stankovic, A.·Gonzalez-Bohorquez, D.·Mallona, I.·Quiniou, M.·Jaeger, B.·Korobeynyk, V.·Brandi, L.·Guenther, S.·Ruenker, A.·Garthe, A.·Cruz Ochoa, N.·Foldy, C.·Furlan, S.·Kempermann, G.·Robinson, M. D.·Jessberger, S.
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Abstract

Neuronal activation drives activity-dependent gene expression that underlies experience-associated synaptic modifications, learning and memory. Here we show that the histone variant CENP-A, best known for specifying centromere identity, is dynamically regulated by synaptic activity at both the RNA and protein levels in postmitotic neurons. Neuronal activation increases a non-centromeric nuclear pool of CENP-A while leaving centromeric CENP-A levels unchanged. Downregulation of CENP-A selectively reduces the activity-associated non-centromeric pool, impairs activity-dependent induction of immediate-early genes such as FOS and ARC, and disrupts hippocampus-dependent learning and memory. Furthermore, we find that activity-dependent neuronal responses in human embryonic stem cell-derived forebrain organoids similarly require CENP-A. Our results reveal a mitosis-independent, conserved role of CENP-A for driving plasticity in mammalian neurons.

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Stankovic, A., Gonzalez-Bohorquez, D., Mallona, I., Quiniou, M., Jaeger, B., Korobeynyk, V., Brandi, L., Guenther, S., Ruenker, A., Garthe, A., Cruz Ochoa, N., Foldy, C., Furlan, S., Kempermann, G., Robinson, M. D., Jessberger, S.. 2026-07-21. Co-option of CENP-A for activity-induced neuronal plasticity. https://doi.org/10.64898/2026.07.16.738894

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