Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE80345 | GEO | 2017/03/24
SECONDARY ACCESSION(S): PRJNA318634
REPOSITORIES: GEO
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Project description:Agonistic encounters with conspecifics are powerful effectors of future behavior that evoke strong and durable neurobiological responses. We recently identified a deeply conserved “toolkit” of transcription factors (TFs) that respond to social challenge across diverse species in coordination with distinct conserved signatures of energy metabolism and developmental signaling. To further characterize this response and its transcriptional drivers in mice, we examined gene expression and chromatin landscape in the hypothalamus, frontal cortex, and amygdala of socially challenged and control animals over time. The data revealed a complex spatiotemporal pattern of metabolic, neural, and developmental transcriptomic signatures coordinated with significant shifts in the accessibility of distally located regulatory elements. Transcriptional regulatory network and motif analyses revealed an interacting network of TFs correlated with differential gene expression across the tissues and time points we assayed, including the early-acting and conserved regulator of energy metabolism and development, ESRRA. Cell-type deconvolution analysis attributed the early metabolic activity implicated by our transcriptomic analysis primarily to oligodendrocytes and the developmental signal to neurons, and we confirmed the presence of ESRRA in both oligodendrocytes and neurons throughout the brain. To assess the role of this nuclear receptor as an early trigger of this coordinated response, we used chromatin immunoprecipitation to map ESRRA binding sites to a set of genes involved in metabolic regulation and enriched in challenge-associated differentially expressed genes. Together, these data support a rich model linking metabolic and neural responses to social challenge, and identify regulatory drivers with unprecedented tissue and temporal resolution.
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