bioRxiv (Cold Spring Harbor Laboratory)
Ectopic histone clipping in the mouse model of progressive myoclonus epilepsy
August 2020 • Eduard Daura, Saara Tegelberg, Masahito Yoshihara, Christopher B. Jackson, Francesca Simonetti, Katri Aksentjeff, Sini Ezer, Paula Hakala, Shintaro K…
ABSTRACT We establish cystatin B (CSTB) as a regulator of histone H3 tail clipping in murine neural progenitor cells (NPCs) and provide evidence suggesting that epigenetic dysregulation contributes to the early pathogenesis in brain disorders associated with deficient CSTB function. We show that NPCs undergo regulated cleavage of the N-terminal tail of histone H3 at threonine 22 (H3T22) transiently upon induction of differentiation. CSTB-deficient NPCs present premature activation of H3T22 clipping during self-ren…