Excess free histone H3 localizes to centrosomes for proteasome-mediated degradation during mitosis in metazoans

Abstract

The cell tightly controls histone protein levels in order to achieve proper packaging of the genome into chromatin, while avoiding the deleterious consequences of excess free histones. Our accompanying study has shown that a histone modification that loosens the intrinsic structure of the nucleosome, phosphorylation of histone H3 on threonine 118 (H3 T118ph), exists on centromeres and chromosome arms during mitosis. Here, we show that H3 T118ph localizes to centrosomes in humans, flies, and worms during all stages of mitosis. H3 abundance at the centrosome increased upon proteasome inhibition, suggesting that excess free histone H3 localizes to centrosomes for degradation during mitosis. In agreement, we find ubiquitinated H3 specifically during mitosis and within purified centrosomes. These results suggest that targeting of histone H3 to the centrosome for proteasome-mediated degradation is a novel pathway for controlling histone supply, specifically during mitosis.

Histone supply: Multitiered regulation ensures chromatin dynamics throughout the cell cycle

“…Interfering with SLBP, which reduces histone expression in human cells, also results in reduced cell growth and impaired S phase progression (Zhao et al, 2004). Intriguingly, the excess H3 during mitosis localizes to the centrosomes for proteasome-mediated degradation in worms, flies, and human cells (Wike et al, 2016). The cross-talk with the centrosome could hence play a role in preserving chromosome integrity by coordinating different signaling events.…”

Alteração na representação de subpopulações de neurônios no epitélio olfatório de camundongos >i<Ric8b>/i< cKO

“…Nesse período, existe uma fração de histonas ligada a cromatina e outra fração livre (que se ligará a cromatina durante a replicação do DNA). O excesso de histona livre se localiza com centrossomos para degradação mediada por proteassoma(WIKE et al, 2016). Existem muitas células progenitoras no MOE, portanto, é possível que as histonas encontradas na fração CE sejam de células progenitoras que estavam se dividindo, pois nessa fase de divisão celular não há membrana nuclear e as histonas devem eluir na As duas bandas em Tot e CE da Ric8b correspondem a proteína RIC8BFL e a RIC8BΔ9.…”