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Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish

BACKGROUND: Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. RESULTS: We find that laboratory an...

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Autores principales: Román, Angel-Carlos, Vicente-Page, Julián, Pérez-Escudero, Alfonso, Carvajal-González, Jose M., Fernández-Salguero, Pedro M., de Polavieja, Gonzalo G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922312/
https://www.ncbi.nlm.nih.gov/pubmed/29695303
http://dx.doi.org/10.1186/s13059-018-1428-y
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author Román, Angel-Carlos
Vicente-Page, Julián
Pérez-Escudero, Alfonso
Carvajal-González, Jose M.
Fernández-Salguero, Pedro M.
de Polavieja, Gonzalo G.
author_facet Román, Angel-Carlos
Vicente-Page, Julián
Pérez-Escudero, Alfonso
Carvajal-González, Jose M.
Fernández-Salguero, Pedro M.
de Polavieja, Gonzalo G.
author_sort Román, Angel-Carlos
collection PubMed
description BACKGROUND: Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. RESULTS: We find that laboratory and isogenic zebrafish larvae show consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. This behavioral inter-individual variability is reduced when we impair the histone deacetylation pathway. Individuals with high levels of histone H4 acetylation, and specifically H4K12, behave similarly to the average of the population, but those with low levels deviate from it. More precisely, we find a set of genomic regions whose histone H4 acetylation is reduced with the distance between the individual and the average population behavior. We find evidence that this modulation depends on a complex of Yin-yang 1 (YY1) and histone deacetylase 1 (HDAC1) that binds to and deacetylates these regions. These changes are not only maintained at the transcriptional level but also amplified, as most target regions are located near genes encoding transcription factors. CONCLUSIONS: We suggest that stochasticity in the histone deacetylation pathway participates in the generation of genetic-independent behavioral inter-individual variability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-018-1428-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-59223122018-05-07 Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish Román, Angel-Carlos Vicente-Page, Julián Pérez-Escudero, Alfonso Carvajal-González, Jose M. Fernández-Salguero, Pedro M. de Polavieja, Gonzalo G. Genome Biol Research BACKGROUND: Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. RESULTS: We find that laboratory and isogenic zebrafish larvae show consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. This behavioral inter-individual variability is reduced when we impair the histone deacetylation pathway. Individuals with high levels of histone H4 acetylation, and specifically H4K12, behave similarly to the average of the population, but those with low levels deviate from it. More precisely, we find a set of genomic regions whose histone H4 acetylation is reduced with the distance between the individual and the average population behavior. We find evidence that this modulation depends on a complex of Yin-yang 1 (YY1) and histone deacetylase 1 (HDAC1) that binds to and deacetylates these regions. These changes are not only maintained at the transcriptional level but also amplified, as most target regions are located near genes encoding transcription factors. CONCLUSIONS: We suggest that stochasticity in the histone deacetylation pathway participates in the generation of genetic-independent behavioral inter-individual variability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-018-1428-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-25 /pmc/articles/PMC5922312/ /pubmed/29695303 http://dx.doi.org/10.1186/s13059-018-1428-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Román, Angel-Carlos
Vicente-Page, Julián
Pérez-Escudero, Alfonso
Carvajal-González, Jose M.
Fernández-Salguero, Pedro M.
de Polavieja, Gonzalo G.
Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish
title Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish
title_full Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish
title_fullStr Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish
title_full_unstemmed Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish
title_short Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish
title_sort histone h4 acetylation regulates behavioral inter-individual variability in zebrafish
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922312/
https://www.ncbi.nlm.nih.gov/pubmed/29695303
http://dx.doi.org/10.1186/s13059-018-1428-y
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