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PreprintCC BY-NC-NDbioRxiv

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

  • A. Stankovic
  • D. Gonzalez-Bohorquez
  • I. Mallona
  • M. Quiniou
  • B. Jaeger
  • V. Korobeynyk
  • L. Brandi
  • S. Guenther
  • A. Ruenker
  • A. Garthe
  • N. Cruz Ochoa
  • C. Foldy
4 more authors
  • S. Furlan
  • G. Kempermann
  • M. D. Robinson
  • S. Jessberger1
  1. 1University of Zurich
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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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Cite

BibTeXRIS
BibTeX
@misc{stankovic2026cooption,
  title = {{Co-option of CENP-A for activity-induced neuronal plasticity}},
  author = {A. Stankovic and D. Gonzalez-Bohorquez and I. Mallona and M. Quiniou and B. Jaeger and V. Korobeynyk and L. Brandi and S. Guenther and A. Ruenker and A. Garthe and N. Cruz Ochoa and C. Foldy and S. Furlan and G. Kempermann and M. D. Robinson and S. Jessberger},
  howpublished = {bioRxiv},
  year = {2026},
  month = jul,
  doi = {10.64898/2026.07.16.738894},
  url = {https://www.biorxiv.org/content/10.64898/2026.07.16.738894v2},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Co-option of CENP-A for activity-induced neuronal plasticity
AU  - A. Stankovic
AU  - D. Gonzalez-Bohorquez
AU  - I. Mallona
AU  - M. Quiniou
AU  - B. Jaeger
AU  - V. Korobeynyk
AU  - L. Brandi
AU  - S. Guenther
AU  - A. Ruenker
AU  - A. Garthe
AU  - N. Cruz Ochoa
AU  - C. Foldy
AU  - S. Furlan
AU  - G. Kempermann
AU  - M. D. Robinson
AU  - S. Jessberger
PY  - 2026
DA  - 2026/07/16
PB  - bioRxiv
DO  - 10.64898/2026.07.16.738894
UR  - https://www.biorxiv.org/content/10.64898/2026.07.16.738894v2
AB  - 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.
ER  -