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RESEARCH PAPER / 2025-12-11

Age- and cell-type-specific effects of histone variant H2BE in the brain.

Sean Louzon, Emily R Feierman, Qi Qiu, Marissa J Maroni, Camille N Quaye, Roxanne Perez-Tremble, Hao Wu, Erica Korb

Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · pubmed

Abstract

Transcription is regulated in part through histone proteins. Histones can be replaced with variant forms that are particularly critical in the brain and accumulate throughout the lifespan. Recent findings demonstrated that the histone variant H2BE regulates chromatin structure, neuronal transcription, and mouse behavior. However, the role of H2BE in other cell types and throughout the lifespan remains unknown. Here, we discovered that H2BE is enriched in astrocytes and accumulates with age in both astrocytes and neurons. Further, we found that H2BE promotes synaptic gene expression in young neurons and astrocytes and is critical in both cell types for proper synaptic function. In aging brains, loss of H2BE similarly affects synaptic genes in neurons but dampens age-related transcriptional changes in both astrocytes and neurons. Lastly, H2BE loss disrupts long-term memory but improves working memory in aging mice. Together, these data link histone variants with aging-related gene-expression changes in both astrocytes and neurons.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that the histone variant H2BE regulates synaptic gene expression and is critical for synaptic function in aging brains. This research is relevant as it explores the role of histone variants in aging-related gene expression changes, linking chromatin dynamics to the aging process in the brain.

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