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. | Román et al. Genome Biology 2018 19 55 https s13059-018-1428-y RESEARCH Open Access Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish Angel-Carlos Román1 2 Julián Vicente-Page1 2 Alfonso Pérez-Escudero2 3 Jose M. Carvajal-González4 Pedro M. Fernández-Salguero4 and Gonzalo G. de Polavieja1 2 Abstract 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. Keywords Epigenetics HDAC YY1 Behavior Inter-individual variability Zebrafish Background paternal effects 6 or the different experiences the indi- Classically the phenotypic diversity of a population is viduals obtain by interacting with the environment or considered to be .
