Increasing H2B monoubiquitination improves the transcriptome and memory in the aged hippocampus.

Shannon Kincaid, Gueladouan Setenet, Natalie J Preveza, Kaiser C Arndt, Phillip Gwin, Yu Lin, Hehuang Xie, Timothy J Jarome

School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA 24061. · pubmed

Paper

Abstract

A decline in cognitive abilities is associated with the aging process, affecting nearly 33% of U.S. adults over the age of 70, and is a risk factor for the development of dementia and Alzheimer's disease. Several studies have reported age-related alterations in the transcriptome in the hippocampus, a major site of memory storage that is among the first regions impacted with age, dementia and Alzheimer's disease. However, much remains unknown about why these transcriptional changes exist in the aged hippocampus and how this impacts memory late in life. Here, we show that monoubiquitination of histone H2B (H2Bubi), an epigenetic mechanism recently reported to be major regulator of the epigenome and transcriptome during memory formation in the young adult brain, decreases with age in the hippocampus of male rats. In vivo CRISPR-dCas9 mediated upregulation of

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Research summary

Increasing H2B monoubiquitination enhances the transcriptome and memory in the aged hippocampus. This research addresses the underlying mechanisms of cognitive decline associated with aging, which is crucial for understanding and potentially mitigating age-related memory impairments.

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