High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases

Clinical Epigenetics
Daniel NättAnnika Thorsell

Abstract

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. 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. Our results show that stress in preschool children leads to changes in DNA methylation similar to those seen in biological aging. We suggest that thi...Continue Reading

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Citations

Nov 26, 2015·International Journal of Alzheimer's Disease·Paul J Couto, Richard M Millis
Jun 11, 2016·International Journal of Psychiatry in Medicine·Eve G SprattCarol Wagner
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Nov 20, 2020·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·Orapan PoachanukoonSittichai Koontongkaew
Jun 5, 2021·Epigenetics & Chromatin·Xena Giada Pappalardo, Viviana Barra

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Datasets Mentioned

BETA
EGAS00001001099

Methods Mentioned

BETA
immunoprecipitation
MeDIP-seq
PCR
SeT
ChIP-seq

Software Mentioned

GenometriCorr R package
UCSC table browser
TOMTOM
RepeatMasker
FIMO
R
MEME
FastQ
CASAVA
Bioconductor

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