PT - JOURNAL ARTICLE AU - Wee, Caroline L. AU - Teo, Shaun AU - Oey, Nicodemus E. AU - Wright, Graham D. AU - VanDongen, Hendrika M.A. AU - VanDongen, Antonius M.J. TI - Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation AID - 10.1523/ENEURO.0019-14.2014 DP - 2014 Nov 01 TA - eneuro PG - ENEURO.0019-14.2014 VI - 1 IP - 1 4099 - http://www.eneuro.org/content/1/1/ENEURO.0019-14.2014.short 4100 - http://www.eneuro.org/content/1/1/ENEURO.0019-14.2014.full SO - eneuro2014 Nov 01; 1 AB - 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 β-spectrin isoform βSpIVΣ5 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 βSpIVΣ5 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.