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Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3)
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 w...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596143/ https://www.ncbi.nlm.nih.gov/pubmed/26464963 http://dx.doi.org/10.1523/ENEURO.0019-14.2014 |
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author | Wee, Caroline L. Teo, Shaun Oey, Nicodemus E. Wright, Graham D. VanDongen, Hendrika M.A. VanDongen, Antonius M.J. |
author_facet | Wee, Caroline L. Teo, Shaun Oey, Nicodemus E. Wright, Graham D. VanDongen, Hendrika M.A. VanDongen, Antonius M.J. |
author_sort | Wee, Caroline L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4596143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-45961432015-10-13 Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) Wee, Caroline L. Teo, Shaun Oey, Nicodemus E. Wright, Graham D. VanDongen, Hendrika M.A. VanDongen, Antonius M.J. eNeuro New Research 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. Society for Neuroscience 2014-11-12 /pmc/articles/PMC4596143/ /pubmed/26464963 http://dx.doi.org/10.1523/ENEURO.0019-14.2014 Text en Copyright © 2014 Wee et al. http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License Attribution-Noncommercial 4.0 International (http://creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial reuse provided that the original work is properly attributed. |
spellingShingle | New Research Wee, Caroline L. Teo, Shaun Oey, Nicodemus E. Wright, Graham D. VanDongen, Hendrika M.A. VanDongen, Antonius M.J. Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) |
title | Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) |
title_full | Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) |
title_fullStr | Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) |
title_full_unstemmed | Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) |
title_short | Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation(1,2,3) |
title_sort | nuclear arc interacts with the histone acetyltransferase tip60 to modify h4k12 acetylation(1,2,3) |
topic | New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596143/ https://www.ncbi.nlm.nih.gov/pubmed/26464963 http://dx.doi.org/10.1523/ENEURO.0019-14.2014 |
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