Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish

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.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1428-y) contains supplementary material, which is available to authorized users.

Emergence of consistent intra-individual locomotor patterns during zebrafish development

“…Our data additionally suggests that the consistency of an individual’s locomotor behavior is not linked to a specific genetic background of an inbred wildtype strain but can be observed in mixed wildtype larvae with genetically more diverse backgrounds. These conclusions are supported by previous research showing that swimming behavior is predictable between individuals when swimming freely in identical wells 41 . Roman et al .…”

“…Secondly, the radial index, which indicates the location of a larva within the well and is calculated based on the distance of a larva from the center of the well, with large values representing proximity to the wall of the well and small values representing a more central location within the well. Although the activity and radial indices have been shown to be independent of one another 41 , our data indicates that the time at which an experiment is performed can influence this apparent independence (Supp. Table 1).…”

“…Behavioral inter-individual variability, as well as inter-strain variability, are increasingly reported for laboratory strains of zebrafish kept for long periods of time 44–49 . Besides genetic diversity, developmental 50,51 , maternal 52,53 and epigenetic effects 41,54,55 , as well as social interactions 56 , are all thought to contribute to such variation. Recently, microRNAs (miRNAs) have been shown to play a role in regulating some behaviors in Drosophila 57–59 and zebrafish 60 , potentially providing another source of behavioral variation.…”

“…To prevent biases introduced through data processing, the same processing settings were applied to data from different days, times and replicates. To characterize the swimming behaviors during the spontaneous, dark and light intervals, the activity and radial index were calculated 41 . The activity index represents the percentage of movement by each larva over one-second intervals and was calculated using a threshold of 2.00 to 1.75 cm/s.…”

Widespread inter‐individual gene expression variability in Arabidopsis thaliana

“…Plants are a promising system to examine the global properties of noise in gene expression, as phenotypic variability, also referred to as phenotypic instability, has been observed in multiple areas of plant growth and development. Inter-individual phenotypic variability has also been observed in isogenic populations of other organisms (Zhang et al, 2016;Roman et al, 2018), but the model plant Arabidopsis thaliana presents the advantage of being an inbreeding species where heterozygosity is extremely low (Abbott & Gomes, 1989). Phenotypic variability in plants can occur both within and between individuals that are growing in the same conditions.…”