Histone H3 lysine 4 methylation signature associated with human undernutrition.
Robin UchiyamaKristyna KupkovaSavera J ShettyAlicia S LinfordMarilyn G Pray-GrantLisa E WagarMark M DavisRashidul HaqueAlban GaultierMarty W MayoPatrick A GrantWilliam A PetriStefan BekiranovDavid T AublePublished in: Proceedings of the National Academy of Sciences of the United States of America (2018)
Chronically undernourished children become stunted during their first 2 years and thereafter bear burdens of ill health for the rest of their lives. Contributors to stunting include poor nutrition and exposure to pathogens, and parental history may also play a role. However, the epigenetic impact of a poor environment on young children is largely unknown. Here we show the unfolding pattern of histone H3 lysine 4 trimethylation (H3K4me3) in children and mothers living in an urban slum in Dhaka, Bangladesh. A pattern of chromatin modification in blood cells of stunted children emerges over time and involves a global decrease in methylation at canonical locations near gene start sites and increased methylation at ectopic sites throughout the genome. This redistribution occurs at metabolic and immune genes and was specific for H3K4me3, as it was not observed for histone H3 lysine 27 acetylation in the same samples. Methylation changes in stunting globally resemble changes that occur in vitro in response to altered methylation capacity, suggesting that reduced levels of one-carbon nutrients in the diet play a key role in stunting in this population. A network of differentially expressed genes in stunted children reveals effects on chromatin modification machinery, including turnover of H3K4me3, as well as posttranscriptional gene regulation affecting immune response pathways and lipid metabolism. Consistent with these changes, reduced expression of the endocytic receptor gene LDL receptor 1 (LRP1) is a driver of stunting in a mouse model, suggesting a target for intervention.
Keyphrases
- genome wide
- dna methylation
- young adults
- immune response
- copy number
- mouse model
- gene expression
- physical activity
- randomized controlled trial
- healthcare
- dna damage
- genome wide identification
- endothelial cells
- mental health
- induced apoptosis
- poor prognosis
- transcription factor
- weight loss
- bone mineral density
- toll like receptor
- endoplasmic reticulum stress
- oxidative stress
- cell proliferation
- climate change
- long non coding rna
- cell cycle arrest
- cell death
- health promotion