RT Journal Article
SR Electronic
T1 Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation
JF eneuro
JO eneuro
FD Society for Neuroscience
SP ENEURO.0019-14.2014
DO 10.1523/ENEURO.0019-14.2014
VO 1
IS 1
A1 Caroline L. Wee
A1 Shaun Teo
A1 Nicodemus E. Oey
A1 Graham D. Wright
A1 Hendrika M.A. VanDongen
A1 Antonius M.J. VanDongen
YR 2014
UL http://www.eneuro.org/content/1/1/ENEURO.0019-14.2014.abstract
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.