Mar 26, 2016

Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children

Molecular Systems Biology
Tobias BauerIrina Lehmann

Abstract

Epigenetic mechanisms have emerged as links between prenatal environmental exposure and disease risk later in life. Here, we studied epigenetic changes associated with maternal smoking at base pair resolution by mapping DNA methylation, histone modifications, and transcription in expectant mothers and their newborn children. We found extensive global differential methylation and carefully evaluated these changes to separate environment associated from genotype-related DNA methylation changes. Differential methylation is enriched in enhancer elements and targets in particular "commuting" enhancers having multiple, regulatory interactions with distal genes. Longitudinal whole-genome bisulfite sequencing revealed that DNA methylation changes associated with maternal smoking persist over years of life. Particularly in children prenatal environmental exposure leads to chromatin transitions into a hyperactive state. Combined DNA methylation, histone modification, and gene expression analyses indicate that differential methylation in enhancer regions is more often functionally translated than methylation changes in promoters or non-regulatory elements. Finally, we show that epigenetic deregulation of a commuting enhancer targeting c-J...Continue Reading

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  • Citations23

References

Mentioned in this Paper

MAP2K1 protein, human
Study
Hydrogen sulfite
DNA Methylation [PE]
MAPK9 protein, human
Protein Methylation
Genome
Transcription, Genetic
MAPK9 wt Allele
Genomic Stability

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