In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood.
Louis LegoffShereen Cynthia D'CruzKatia BouchekhchoukhaChristine MonfortChristian JaulinLuc MultignerFatima SmagulovaPublished in: Life science alliance (2021)
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.
Keyphrases
- cord blood
- genome wide
- endothelial cells
- dna methylation
- cell cycle
- induced pluripotent stem cells
- dna repair
- gene expression
- immune response
- pluripotent stem cells
- cell proliferation
- dna damage
- autism spectrum disorder
- poor prognosis
- copy number
- long non coding rna
- induced apoptosis
- oxidative stress
- pi k akt
- deep learning
- cell death
- estrogen receptor
- early life
- genome wide identification
- intellectual disability
- big data