Format

Send to

Choose Destination

See 1 citation:

Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1219-1228. doi: 10.1073/pnas.1811758115. Epub 2018 Dec 11.

Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques.

Author information

1
Department of Evolutionary Anthropology, Duke University, Durham, NC 27708; nsmack@uw.edu jt5@duke.edu.
2
Duke Center for the Study of Aging and Human Development, Duke University, Durham, NC 27708.
3
Department of Biochemistry, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada H3T 1J4.
4
Department of Genetics, CHU Sainte-Justine Research Center, Montreal, QC, Canada H3T 1C5.
5
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322.
6
Department of Evolutionary Anthropology, Duke University, Durham, NC 27708.
7
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201.
8
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201.
9
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322.
10
Department of Pediatrics, Faculty of Medicine, Université de Montréal, QC, Canada H3T 1J4.
11
Department of Biology, Duke University, Durham, NC 27708.
12
Institute of Primate Research, National Museums of Kenya, 00502 Nairobi, Kenya.
13
Duke Population Research Institute, Duke University, Durham, NC 27708.

Abstract

Low social status is an important 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. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used an in vitro GC challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We 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 motifs for the GC receptor cofactor 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 mechanism involved in social stress-driven 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.

KEYWORDS:

chromatin accessibility; dominance rank; epigenomics; gene regulation; social status

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center