Abstract
Environmental factors can induce detrimental consequences into adulthood life. In this study, we examined the epigenetic effects induced by in utero chlordecone (CD) exposure on human male cord blood as well as in blood-derived Ke-37 cell line. Genome-wide analysis of histone H3K4me3 distribution revealed that genes related to chromosome segregation, chromatin organization, and cell cycle have altered occupancy in their promoters. The affected regions were enriched in ESR1, SP family, and IKZF1 binding motifs. We also observed a global reduction in H3K9me3, markedly in repeated sequences of the genome. Decrease in H3K9me3 after CD exposure correlates with decreased methylation in LINE-1 promoters and telomere length extension. These observations on human cord blood were assessed in the Ke-37 human cell line. H3K4me3 and the expression of genes related to immune response, DNA repair, and chromatin organization, which were affected in human cord blood were also altered in CD-exposed Ke-37 cells. Our data suggest that developmental exposure to CD leads to profound changes in histone modification patterns and affects the processes controlled by them in human cord blood.
Highlights
The Developmental Origins of Health and Disease concept postulates that exposure to certain environmental factors during critical period of development and growth may have significant consequences on an individual’s short- and long-term health [1]
DNA methylation changes were detected in the vicinity of genes related to oxidative stress response, the cytochrome P450 family 1 subfamily A member 1 (CYP1A1), transport, metabolism, transcription and signaling, contactin associated protein 1 (CNTNAP), SH3 and multiple ankyrin repeat domains 2 (SHANK2), and tripartite motif containing 36 (TRIM36) [6,7]
We analyzed histone H3K4me3 occupancy at the genomewide level, telomere length copy number variations and LINE L1 DNA methylation changes by using genomic DNA from cord blood samples. For these human cord blood studies, given the limited amount of material, global amounts of H3K4me3, H3K9me3, and H4Ac were determined by the immunofluorescence method using structurally preserved nuclei (SPN) slides
Summary
The Developmental Origins of Health and Disease concept postulates that exposure to certain environmental factors during critical period of development and growth may have significant consequences on an individual’s short- and long-term health [1]. Exposure to toxic substances during both critical reprogramming windows leads to profound changes in somatic and germ cells. The authors summarized a large number of publications wherein the effects of several pollutants such as aflatoxin B1, arsenic, bisphenol A (BPA), polycyclic aromatic hydrocarbons, tobacco smoke, and nutritional factors on genomic DNA methylation state were measured [3]. DNA methylation changes were detected in the vicinity of genes related to oxidative stress response (aryl-hydrocarbon receptor repressor [AHRR]), the cytochrome P450 family 1 subfamily A member 1 (CYP1A1), transport (myosin IG [MYO1G]), metabolism (acyl-CoA synthetase medium chain family member 3 [ACSM3]), transcription and signaling (growth factor independent 1 transcriptional repressor [GFI1]), contactin associated protein 1 (CNTNAP), SH3 and multiple ankyrin repeat domains 2 (SHANK2), and tripartite motif containing 36 (TRIM36) [6,7]. It was suggested that changes in DNA methyltransferase enzyme activity could be a major cause for differential DNA methylation [3]
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