Journal
ENEURO
Volume 1, Issue 1, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0019-14.2014
Keywords
chromatin modification; epigenetics; histone acetylation; immediate early gene; synaptic plasticity
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Funding
- Singapore Ministry of Education [MOE2012-T2-1-039]
- Singapore Ministry of Health
- A*STAR
- Agency for Science, Technology and Research
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Arc is an immediate-early gene whose genetic ablation selectively abrogates long-term memory, indicating a critical role in memory consolidation. Although Arc protein is found at synapses, it also localizes to the neuronal nucleus, where its function is less understood. Nuclear Arc forms a complex with the beta-spectrin isoform beta SpIV Sigma 5 and associates with PML bodies, sites of epigenetic regulation of gene expression. We report here a novel interaction between Arc and Tip60, a histone-acetyltransferase and subunit of a chromatin-remodelling complex, using biochemistry and super-resolution microscopy in primary rat hippocampal neurons. Arc and beta SpIV Sigma 5 are recruited to nuclear Tip60 speckles, and the three proteins form a tight complex that localizes to nuclear perichromatin regions, sites of transcriptional activity. Neuronal activity-induced expression of Arc (1) increases endogenous nuclear Tip60 puncta, (2) recruits Tip60 to PML bodies, and (3) increases histone acetylation of Tip60 substrate H4K12, a learning-induced chromatin modification. These mechanisms point to an epigenetic role for Arc in regulating memory consolidation.
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