RT Journal Article SR Electronic T1 Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish JF bioRxiv FD Cold Spring Harbor Laboratory SP 100230 DO 10.1101/100230 A1 Angel-Carlos Román A1 Julián Vicente-Page A1 Alfonso Pérez-Escudero A1 Jose M. Carvajal-González A1 Pedro M. Fernández-Salguero A1 Gonzalo G. de Polavieja YR 2017 UL http://biorxiv.org/content/early/2017/08/06/100230.abstract AB Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We found that laboratory and isogenic zebrafish (Danio rerio) larvae showed consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. We also found that this behavioral inter-individual variability was reduced when we impaired the histone deacetylation pathway. Individuals with high levels of histone H4 acetylation, and specifically H4K12, behaved similar to the average of the population, but those with low levels deviated from it. More precisely, we found a set of genomic regions whose histone H4 acetylation is reduced with the distance between the individual and the average population behavior. We found 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 were not only maintained at the transcriptional level but also amplified, as most target regions were located near genes encoding transcription factors. We suggest that stochasticity in the histone deacetylation pathway participates the generation of genetic-independent behavioral inter-individual variability.