Globally elevated levels of histone H3 lysine 9 trimethylation in early infancy are associated with poor growth trajectory in Bangladeshi children

Clinical Epigenetics

Research

Savera J. Shetty¹  David T. Auble¹  Kristyna Kupkova²  Marilyn G. Pray-Grant³  Patrick A. Grant³  William A. Petri⁴  Rashidul Haque⁵ 

[1] Department of Biochemistry and Molecular Genetics, University of Virginia Health System, 22908, Charlottesville, VA, USA;Department of Biochemistry and Molecular Genetics, University of Virginia Health System, 22908, Charlottesville, VA, USA;Center for Public Health Genomics, University of Virginia Health System, 22908, Charlottesville, VA, USA;Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 33431, Boca Raton, FL, USA;Division of Infectious Diseases and International Health, University of Virginia Health System, 22908, Charlottesville, VA, USA;Infectious Disease Division, International Centre for Diarrhoeal Disease Research, 1000, Dhaka, Bangladesh;

关键词: Stunting;    Childhood undernutrition;    Epigenetics;    Histone methylation;    Heterochromatin;    Endogenous retroviruses;   

DOI  :  10.1186/s13148-023-01548-z

 received in 2022-12-15, accepted in 2023-08-06,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundStunting 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.ResultsWe 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.ConclusionsWe 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 3

13690_2023_1151_Article_IEq24.gif

40517_2023_266_Article_IEq34.gif

40517_2023_266_Article_IEq15.gif

Fig. 6

Fig. 5

Fig. 3