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DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation
Numerous studies have shown that following retrieval, a previously consolidated memory requires increased transcriptional regulation in order to be reconsolidated. Previously, it was reported that histone H3 lysine-4 trimethylation (H3K4me3), a marker of active transcription, is increased in the hip...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730899/ https://www.ncbi.nlm.nih.gov/pubmed/33256213 http://dx.doi.org/10.3390/ijms21238995 |
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author | Navabpour, Shaghayegh Rogers, Jessie McFadden, Taylor Jarome, Timothy J. |
author_facet | Navabpour, Shaghayegh Rogers, Jessie McFadden, Taylor Jarome, Timothy J. |
author_sort | Navabpour, Shaghayegh |
collection | PubMed |
description | Numerous studies have shown that following retrieval, a previously consolidated memory requires increased transcriptional regulation in order to be reconsolidated. Previously, it was reported that histone H3 lysine-4 trimethylation (H3K4me3), a marker of active transcription, is increased in the hippocampus after the retrieval of contextual fear memory. However, it is currently unknown how this epigenetic mark is regulated during the reconsolidation process. Furthermore, though recent evidence suggests that neuronal activity triggers DNA double-strand breaks (DSBs) in some early-response genes, it is currently unknown if DSBs contribute to the reconsolidation of a memory following retrieval. Here, using chromatin immunoprecipitation (ChIP) analyses, we report a significant overlap between DSBs and H3K4me3 in area CA1 of the hippocampus during the reconsolidation process. We found an increase in phosphorylation of histone H2A.X at serine 139 (H2A.XpS139), a marker of DSB, in the Npas4, but not c-fos, promoter region 5 min after retrieval, which correlated with increased H3K4me3 levels, suggesting that the two epigenetic marks may work in concert during the reconsolidation process. Consistent with this, in vivo siRNA-mediated knockdown of topoisomerase II β, the enzyme responsible for DSB, prior to retrieval, reduced Npas4 promoter-specific H2A.XpS139 and H3K4me3 levels and impaired long-term memory, indicating an indispensable role of DSBs in the memory reconsolidation process. Collectively, our data propose a novel mechanism for memory reconsolidation through increases in epigenetic-mediated transcriptional control via DNA double-strand breaks. |
format | Online Article Text |
id | pubmed-7730899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77308992020-12-12 DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation Navabpour, Shaghayegh Rogers, Jessie McFadden, Taylor Jarome, Timothy J. Int J Mol Sci Article Numerous studies have shown that following retrieval, a previously consolidated memory requires increased transcriptional regulation in order to be reconsolidated. Previously, it was reported that histone H3 lysine-4 trimethylation (H3K4me3), a marker of active transcription, is increased in the hippocampus after the retrieval of contextual fear memory. However, it is currently unknown how this epigenetic mark is regulated during the reconsolidation process. Furthermore, though recent evidence suggests that neuronal activity triggers DNA double-strand breaks (DSBs) in some early-response genes, it is currently unknown if DSBs contribute to the reconsolidation of a memory following retrieval. Here, using chromatin immunoprecipitation (ChIP) analyses, we report a significant overlap between DSBs and H3K4me3 in area CA1 of the hippocampus during the reconsolidation process. We found an increase in phosphorylation of histone H2A.X at serine 139 (H2A.XpS139), a marker of DSB, in the Npas4, but not c-fos, promoter region 5 min after retrieval, which correlated with increased H3K4me3 levels, suggesting that the two epigenetic marks may work in concert during the reconsolidation process. Consistent with this, in vivo siRNA-mediated knockdown of topoisomerase II β, the enzyme responsible for DSB, prior to retrieval, reduced Npas4 promoter-specific H2A.XpS139 and H3K4me3 levels and impaired long-term memory, indicating an indispensable role of DSBs in the memory reconsolidation process. Collectively, our data propose a novel mechanism for memory reconsolidation through increases in epigenetic-mediated transcriptional control via DNA double-strand breaks. MDPI 2020-11-26 /pmc/articles/PMC7730899/ /pubmed/33256213 http://dx.doi.org/10.3390/ijms21238995 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Navabpour, Shaghayegh Rogers, Jessie McFadden, Taylor Jarome, Timothy J. DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation |
title | DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation |
title_full | DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation |
title_fullStr | DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation |
title_full_unstemmed | DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation |
title_short | DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation |
title_sort | dna double-strand breaks are a critical regulator of fear memory reconsolidation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730899/ https://www.ncbi.nlm.nih.gov/pubmed/33256213 http://dx.doi.org/10.3390/ijms21238995 |
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