Abstract
BackgroundAnimals 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.ResultsWe 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.ConclusionsWe suggest that stochasticity in the histone deacetylation pathway participates in the generation of genetic-independent behavioral inter-individual variability.
Highlights
Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive
We found that behavioral interindividual variability of zebrafish larvae is independent of the genetic differences but it is correlated to histone H4 acetylation levels in a specific set of genomic sequences and regulated by a molecular complex composed by at least Yin-yang 1 (YY1) and histone deacetylase 1 (HDAC1)
We found that NaBu treatment did not further decrease the behavioral inter-individual variability of the yy1 +/− fish (P = 0.54, permutation test), while the double heterozygotic mutation was lethal to the animals
Summary
Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. Our knowledge about behavioral variability independent of genetic differences has increased substantially, but its underlying mechanisms remain unclear. Neuronal changes such as neurogenesis or serotonin signaling have been shown to be final targets of behavioral individuality [3, 4], but the molecular mechanisms required to develop these differences are still unknown. DNA methylation differences have been associated with behavioral castes in honeybees [7], and they are necessary and sufficient to mediate social defeat stress [8] Histone acetylation is another of the main epigenetic modifications [9] and it has been shown to regulate different behaviors such as mating preference in prairie
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