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.
Show 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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