Histone H3 lysine 4 methylation signature associated with human undernutrition

journal article in Web of Science

English

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 s

epigenetics, undernutrition, histone methylation

UCHIYAMA, R.; KUPKOVÁ, K.; SHETTY, S.; LINFORD, A.; PRAY-GRANT, M.; WAGAR, L.; DAVIS, M.; HAQUE, R.; GAULTIER, A.; MAYO, M.; GRANT, P.; PETRI, W.; BEKIRANOV, S.; AUBLE, D.

12. 11. 2018

Proceedings of the National Academy of Sciences

USA

0027-8424

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

115

48

United States of America

E11264

E11273

10

http://www.pnas.org/content/115/48/E11264