High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases.
BACKGROUND
Childhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic link prospectively in children.


RESULTS
Here, we studied a homogenous group of 48 5-year-old children. By combining hair cortisol measurements (a well-documented biomarker for chronic stress), with whole-genome DNA-methylation sequencing, we show that high cortisol associates with a genome-wide decrease in DNA methylation and targets short interspersed nuclear elements (SINEs; a type of retrotransposon) and genes important for calcium transport: phenomena commonly affected in stress-related diseases and in biological aging. More importantly, we identify a zinc-finger transcription factor, ZNF263, whose binding sites where highly overrepresented in regions experiencing methylation loss. This type of zinc-finger protein has previously shown to be involved in the defense against retrotransposons.


CONCLUSIONS
Our results show that stress in preschool children leads to changes in DNA methylation similar to those seen in biological aging. We suggest that this may affect future disease susceptibility by alterations in the epigenetic mechanisms that keep retrotransposons dormant. Future treatments for stress- and age-related diseases may therefore seek to target zinc-finger proteins that epigenetically control retrotransposon reactivation, such as ZNF263.
Department of Clinical and Experimental Medicine, Division of Cell Biology, Linkoping University, Linkoping, 58183 Sweden.
Daniel
0000-0001-9182-9401
D
Nätt
Department of Clinical and Experimental Medicine, Division of Pediatrics, Linkoping University, Linkoping, 58183 Sweden.
Ingela
I
Johansson
Department of Medicine and Health Sciences, Community Medicine/General Practice, Linkoping University, Linkoping, 58183 Sweden.
Tomas
T
Faresjö
Department of Clinical and Experimental Medicine, Division of Pediatrics, Linkoping University, Linkoping, 58183 Sweden.
Johnny
J
Ludvigsson
Department of Clinical and Experimental Medicine, Division of Cell Biology, Linkoping University, Linkoping, 58183 Sweden.
Annika
A
Thorsell
Blood; Children; Cortisol; DNA methylation; EGR1; Hair; Retrotransposon; Stress; Transcription factor; ZNF263