Globally elevated levels of histone H3 lysine 9 trimethylation in early infancy are associated with poor growth trajectory in Bangladeshi children
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Published:2023-08-11
Issue:1
Volume:15
Page:
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ISSN:1868-7083
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Container-title:Clinical Epigenetics
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language:en
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Short-container-title:Clin Epigenet
Author:
Kupkova Kristyna,Shetty Savera J.,Pray-Grant Marilyn G.,Grant Patrick A.,Haque Rashidul,Petri William A.,Auble David T.
Abstract
Abstract
Background
Stunting is a global health problem affecting hundreds of millions of children worldwide and contributing to 45% of deaths in children under the age of five. Current therapeutic interventions have limited efficacy. Understanding the epigenetic changes underlying stunting will elucidate molecular mechanisms and likely lead to new therapies.
Results
We profiled the repressive mark histone H3 lysine 9 trimethylation (H3K9me3) genome-wide in peripheral blood mononuclear cells (PBMCs) from 18-week-old infants (n = 15) and mothers (n = 14) enrolled in the PROVIDE study established in an urban slum in Bangladesh. We associated H3K9me3 levels within individual loci as well as genome-wide with anthropometric measurements and other biomarkers of stunting and performed functional annotation of differentially affected regions. Despite the relatively small number of samples from this vulnerable population, we observed globally elevated H3K9me3 levels were associated with poor linear growth between birth and one year of age. A large proportion of the differentially methylated genes code for proteins targeting viral mRNA and highly significant regions were enriched in transposon elements with potential regulatory roles in immune system activation and cytokine production. Maternal data show a similar trend with child’s anthropometry; however, these trends lack statistical significance to infer an intergenerational relationship.
Conclusions
We speculate that high H3K9me3 levels may result in poor linear growth by repressing genes involved in immune system activation. Importantly, changes to H3K9me3 were detectable before the overt manifestation of stunting and therefore may be valuable as new biomarkers of stunting.
Funder
Biomedical Sciences Graduate Program, University of Virginia
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
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