DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation

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dc.contributor.authorNavabpour, Shaghayeghen
dc.contributor.authorRogers, Jessieen
dc.contributor.authorMcFadden, Tayloren
dc.contributor.authorJarome, Timothy J.en
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentSchool of Neuroscienceen
dc.date.accessioned2020-12-10T19:42:54Zen
dc.date.available2020-12-10T19:42:54Zen
dc.date.issued2020-11-26en
dc.date.updated2020-12-10T14:10:54Zen
dc.description.abstractNumerous 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 <i>Npas4</i>, but not <i>c-fos</i>, 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 &beta;, the enzyme responsible for DSB, prior to retrieval, reduced <i>Npas4</i> 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationNavabpour, S.; Rogers, J.; McFadden, T.; Jarome, T.J. DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation. Int. J. Mol. Sci. 2020, 21, 8995.en
dc.identifier.doihttps://doi.org/10.3390/ijms21238995en
dc.identifier.urihttp://hdl.handle.net/10919/101065en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectepigeneticen
dc.subjecthistone methylationen
dc.subjectDNA double-strand breaksen
dc.subjectMemoryen
dc.subjectreconsolidationen
dc.subjectretrievalen
dc.subjecthippocampusen
dc.titleDNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidationen
dc.title.serialInternational Journal of Molecular Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)
Destination Area: Adaptive Brain and Behavior (ABB)
Scholarly Works, Biological Sciences
Scholarly Works, Fralin Biomedical Research Institute at VTC
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