BioProject

Social status is a major predictor of disease susceptibility and mortality risk in humans and other social mammals. More...

Social status is a major predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response, notably GC resistance during chronic stress, although the underlying molecular mechanisms remain elusive. Here, we used an in vitro glucocorticoid challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for GC-related immune cell gene regulation in female rhesus macaques, using paired (control and GC-treated) peripheral blood mononuclear cell samples. Our results show that social status not only influences immune cell gene expression, but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression after GC exposure. Regions that were more accessible in high status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including binding sites for the glucocorticoid receptor co-factor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation, and identify chromatin accessibility as a potential mechanism involved in social stress-associated GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor. Less...