Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3).
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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 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.
Published Version (Please cite this version)10.1523/ENEURO.0019-14.2014
Publication InfoOey, N; Teo, S; VanDongen, Antonius MJ; VanDongen, H; Wee, C; & Wright, G (2014). Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3). eNeuro, 1(1). 10.1523/ENEURO.0019-14.2014. Retrieved from http://hdl.handle.net/10161/15436.
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Associate Professor of Pharmacology & Cancer Biology
Ion channels are complex integral membrane proteins that serve many physiological roles. Our primary objective is to understand how ion channels function, at both the molecular and cellular level. For this aim we employ two model systems: drk1 (Kv2.1), a voltage-gated K channel expressed in the central nervous system and the heart, and the NMDA receptor, a member of the ionotropic glutamte receptor family critically involved in learning and memory. The relationship