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Altered histone acetylation is associated with age-dependent memory impairment in mice

Official URL:https://doi.org/10.1126/science.1186088
PubMed:View item in PubMed
Creators Name:Peleg, S. and Sananbenesi, F. and Zovoilis, A. and Burkhardt, S. and Bahari-Javan, S. and Agis-Balboa, R.C. and Cota, P. and Wittnam, J.L. and Gogol-Doering, A. and Opitz, L. and Salinas-Riester, G. and Dettenhofer, M. and Kang, H. and Farinelli, L. and Chen, W. and Fischer, A.
Journal Title:Science
Journal Abbreviation:Science
Volume:328
Number:5979
Page Range:753-756
Date:7 May 2010
Keywords:Acetylation, Aging, Chromatin, Chromatin Assembly and Disassembly, Conditioning, Genetic Epigenesis, Fear, Gene Expression Profiling, Gene Expression Regulation, Hippocampus, Histone Deacetylase Inhibitors, Histones, Hydroxamic Acids, Learning, Lysine, Memory, Memory Disorders, Microfilament Proteins, Nuclear Proteins, Signal Transduction, Transcription Initiation Site, Genetic Transcription, Up-Regulation, Animals, Mice
Abstract:As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.
ISSN:0036-8075
Publisher:American Association for the Advancement of Science (U.S.A.)
Item Type:Article

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