Genome-wide effects of social status on DNA methylation in the brain of a cichlid fish, Astatotilapia burtoni

• Published in: BMC genomics Vol. 20; no. 1; p. 699
• Main Authors: Hilliard, Austin T, Xie, Dan, Ma, Zhihai, Snyder, Michael P, Fernald, Russell D
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.09.2019; BioMed Central; BMC
• Subjects: Alternative splicing; Analysis; Animal behavior; Animal social behavior; Animals; Antisense RNA; Astatotilapia burtoni; Behavior; Behavior, Animal; Behavioral plasticity; Brain; Brain - cytology; Brain - metabolism; cichlid fish; Cichlids; Cichlids - genetics; Deoxyribonucleic acid; DNA; DNA binding proteins; DNA Methylation; Fish; GABAergic Neurons - metabolism; Gene expression; Gene Expression Profiling; Gene regulation; Genes; Genetic aspects; Genetic regulation; Genome-wide association studies; Genomes; Genomics; hypothalamus; Hypothalamus - cytology; Hypothalamus - metabolism; Integration; Methylation; Neural plasticity; Novels; Oligodendroglia - metabolism; Physiological aspects; Reproductive system; Signal Transduction - genetics; Social behavior; Social change; Social classes; Social Environment; Social interactions; social status; Substrates; Sulfites; Time integration; Transcription (Genetics); Transcription factors; social status; environment; cichlid fish; gene regulation; neural plasticity; Astatotilapia burtoni; whole genome; DNA methylation; bisulfite sequencing; brain; hypothalamus
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-019-6047-9

Successful social behavior requires real-time integration of information about the environment, internal physiology, and past experience. The molecular substrates of this integration are poorly understood, but likely modulate neural plasticity and gene regulation. In the cichlid fish species Astatotilapia burtoni, male social status can shift rapidly depending on the environment, causing fast behavioral modifications and a cascade of changes in gene transcription, the brain, and the reproductive system. These changes can be permanent but are also reversible, implying the involvement of a robust but flexible mechanism that regulates plasticity based on internal and external conditions. One candidate mechanism is DNA methylation, which has been linked to social behavior in many species, including A. burtoni. But, the extent of its effects after A. burtoni social change were previously unknown. We performed the first genome-wide search for DNA methylation patterns associated with social status in the brains of male A. burtoni, identifying hundreds of Differentially Methylated genomic Regions (DMRs) in dominant versus non-dominant fish. Most DMRs were inside genes supporting neural development, synapse function, and other processes relevant to neural plasticity, and DMRs could affect gene expression in multiple ways. DMR genes were more likely to be transcription factors, have a duplicate elsewhere in the genome, have an anti-sense lncRNA, and have more splice variants than other genes. Dozens of genes had multiple DMRs that were often seemingly positioned to regulate specific splice variants. Our results revealed genome-wide effects of A. burtoni social status on DNA methylation in the brain and strongly suggest a role for methylation in modulating plasticity across multiple biological levels. They also suggest many novel hypotheses to address in mechanistic follow-up studies, and will be a rich resource for identifying the relationships between behavioral, neural, and transcriptional plasticity in the context of social status.