Profiling DNA break sites and transcriptional changes in response to contextual fear learning.

Neuronal activity generates DNA double-strand breaks (DSBs) at specific loci in vitro and this facilitates the rapid transcriptional induction of early response genes (ERGs). Physiological neuronal activity, including exposure of mice to learning behaviors, also cause the formation of DSBs, yet the...

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Autores principales:	Ryan T Stott, Oleg Kritsky, Li-Huei Tsai
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eba25bb316f847acaff9ad4508b107e3
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spelling	oai:doaj.org-article:eba25bb316f847acaff9ad4508b107e32021-12-02T20:05:16ZProfiling DNA break sites and transcriptional changes in response to contextual fear learning.1932-620310.1371/journal.pone.0249691https://doaj.org/article/eba25bb316f847acaff9ad4508b107e32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0249691https://doaj.org/toc/1932-6203Neuronal activity generates DNA double-strand breaks (DSBs) at specific loci in vitro and this facilitates the rapid transcriptional induction of early response genes (ERGs). Physiological neuronal activity, including exposure of mice to learning behaviors, also cause the formation of DSBs, yet the distribution of these breaks and their relation to brain function remains unclear. Here, following contextual fear conditioning (CFC) in mice, we profiled the locations of DSBs genome-wide in the medial prefrontal cortex and hippocampus using γH2AX ChIP-Seq. Remarkably, we found that DSB formation is widespread in the brain compared to cultured primary neurons and they are predominately involved in synaptic processes. We observed increased DNA breaks at genes induced by CFC in neuronal and non-neuronal nuclei. Activity-regulated and proteostasis-related transcription factors appear to govern some of these gene expression changes across cell types. Finally, we find that glia but not neurons have a robust transcriptional response to glucocorticoids, and many of these genes are sites of DSBs. Our results indicate that learning behaviors cause widespread DSB formation in the brain that are associated with experience-driven transcriptional changes across both neuronal and glial cells.Ryan T StottOleg KritskyLi-Huei TsaiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0249691 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryan T Stott Oleg Kritsky Li-Huei Tsai Profiling DNA break sites and transcriptional changes in response to contextual fear learning.
description	Neuronal activity generates DNA double-strand breaks (DSBs) at specific loci in vitro and this facilitates the rapid transcriptional induction of early response genes (ERGs). Physiological neuronal activity, including exposure of mice to learning behaviors, also cause the formation of DSBs, yet the distribution of these breaks and their relation to brain function remains unclear. Here, following contextual fear conditioning (CFC) in mice, we profiled the locations of DSBs genome-wide in the medial prefrontal cortex and hippocampus using γH2AX ChIP-Seq. Remarkably, we found that DSB formation is widespread in the brain compared to cultured primary neurons and they are predominately involved in synaptic processes. We observed increased DNA breaks at genes induced by CFC in neuronal and non-neuronal nuclei. Activity-regulated and proteostasis-related transcription factors appear to govern some of these gene expression changes across cell types. Finally, we find that glia but not neurons have a robust transcriptional response to glucocorticoids, and many of these genes are sites of DSBs. Our results indicate that learning behaviors cause widespread DSB formation in the brain that are associated with experience-driven transcriptional changes across both neuronal and glial cells.
format	article
author	Ryan T Stott Oleg Kritsky Li-Huei Tsai
author_facet	Ryan T Stott Oleg Kritsky Li-Huei Tsai
author_sort	Ryan T Stott
title	Profiling DNA break sites and transcriptional changes in response to contextual fear learning.
title_short	Profiling DNA break sites and transcriptional changes in response to contextual fear learning.
title_full	Profiling DNA break sites and transcriptional changes in response to contextual fear learning.
title_fullStr	Profiling DNA break sites and transcriptional changes in response to contextual fear learning.
title_full_unstemmed	Profiling DNA break sites and transcriptional changes in response to contextual fear learning.
title_sort	profiling dna break sites and transcriptional changes in response to contextual fear learning.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/eba25bb316f847acaff9ad4508b107e3
work_keys_str_mv	AT ryantstott profilingdnabreaksitesandtranscriptionalchangesinresponsetocontextualfearlearning AT olegkritsky profilingdnabreaksitesandtranscriptionalchangesinresponsetocontextualfearlearning AT lihueitsai profilingdnabreaksitesandtranscriptionalchangesinresponsetocontextualfearlearning
_version_	1718375516994535424

Profiling DNA break sites and transcriptional changes in response to contextual fear learning.

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