Acetylation-like H2BK109Q attenuates acute brain injury and preserves axon-myelin integrity after intracerebral hemorrhage.

Authors

Sinan Jin, Meng Yang, Jincheng Meng, Ziyi Han, Yousef Rastegar-Kashkooli, Pengtian Lu, Junmin Wang, Jian Wang, He Wu

Published in

CNS neuroscience & therapeutics. Volume 32. Issue 10. Pages e71172.

Abstract

Axon-myelin damage contributes to neurological dysfunction after intracerebral hemorrhage (ICH), but the upstream chromatin regulators remain unclear. We aimed to characterize the H2B acetylation response to ICH, test the functional significance of modeled H2BK109 states, and identify a downstream effector of H2BK109Q-mediated protection.
Pan-H2B acetylation was examined in mice with collagenase-induced ICH and in hemoglobin-treated HT22 cells, and the histone acetylome of the mouse brain was profiled. H2BK109Q and H2BK109R were used to model acetylation-mimetic and non-acetylated lysine-like states. Injury outcomes, axon-myelin integrity, molecular profiles, and regional Galc knockdown were assessed.
ICH and hemoglobin reduced pan-H2B acetylation, and acetylome profiling indicated reduced H2BK109ac. H2BK109Q-expressing mice showed higher pan-H2B acetylation, smaller hematomas, less edema and apoptosis, improved neurological function, and greater preservation of LFB, MBP, NF200, and axon-myelin ultrastructure. Under matched hemoglobin exposure, H2BK109Q-expressing HT22 cells showed higher BCL2/BAX ratios and lower TUNEL positivity than H2BK109R-expressing cells. In vitro analyses highlighted GALC as a candidate downstream effector of H2BK109Q-associated protection. In H2BK109Q-expressing mice, Galc knockdown reduced LFB- and MBP-positive areas and NF200 signals in the caudate putamen and corpus callosum compared with untreated and siNC controls.
H2BK109Q attenuates acute ICH injury and preserves axon-myelin integrity, with GALC contributing to these protective effects.

PMID:
42851076
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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