Abstract
BackgroundEpigenetic mechanisms play fundamental roles in brain function and behavior and stressors such as social isolation can alter animal behavior via epigenetic mechanisms. However, due to cellular heterogeneity, identifying cell-type-specific epigenetic changes in the brain is challenging. Here, we report the first use of a modified isolation of nuclei tagged in specific cell type (INTACT) method in behavioral epigenetics of Drosophila melanogaster, a method we call mini-INTACT.ResultsUsing ChIP-seq on mini-INTACT purified dopaminergic nuclei, we identified epigenetic signatures in socially isolated and socially enriched Drosophila males. Social experience altered the epigenetic landscape in clusters of genes involved in transcription and neural function. Some of these alterations could be predicted by expression changes of four transcription factors and the prevalence of their binding sites in several clusters. These transcription factors were previously identified as activity-regulated genes, and their knockdown in dopaminergic neurons reduced the effects of social experience on sleep.ConclusionsOur work enables the use of Drosophila as a model for cell-type-specific behavioral epigenetics and establishes that social environment shifts the epigenetic landscape in dopaminergic neurons. Four activity-related transcription factors are required in dopaminergic neurons for the effects of social environment on sleep.
Highlights
Environmental stressors have robust effects on the behavior of animals including humans, rodents, and fruit flies
We found that some genes encoding activity-regulated transcription factors (ARG-TFs) [61] respond to social environment in dopaminergic neurons and that knockdown of the genes encoding four of these activity-related genes” (ARGs)-TFs reduced the effects of social experience on daytime sleep
Results mini-INTACT purifies rare cell types from adult Drosophila brain The INTACT method developed in Drosophila melanogaster expresses a SUN domain protein (UNC84) from C. elegans that localizes green fluorescent protein (GFP) to the inner nuclear membrane [55]
Summary
Environmental stressors have robust effects on the behavior of animals including humans, rodents, and fruit flies. Several studies have implicated dopaminergic neurons in encoding the effects of social isolation in rodents [17, 27, 28], and social isolation has been shown to decrease dopamine levels in flies [11] and mice [25]. Dopaminergic neurons play an important role in Agrawal et al BMC Biology (2019) 17:30 modulating behaviors influenced by social isolation in Drosophila, including aggression [29], sleep [11, 30,31,32,33], and alcohol intoxication [34]. While studies have implicated epigenetic mechanisms in subsets of brain regions and point to a role of dopaminergic neurons in social isolation, it is not known how stressors such as social isolation influence the epigenome in specific cell types of the brain and thereby affect behavior. We report the first use of a modified isolation of nuclei tagged in specific cell type (INTACT) method in behavioral epigenetics of Drosophila melanogaster, a method we call mini-INTACT
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