Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease

Epigenetics & Chromatin
Michael K SkinnerWei Yan

Abstract

Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm. Gestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated. DNA methylation and ncRNA were altered in each generation sperm with the direct exposure F1 and F2 generations being predominantly distinct from the F3 generation epimutations. The piRNA and small tRNA were the most predominant classes of ncRNA altered. A highly conserved set of histone retention sites were found in the control lineage generations which was not significantly altered between generations, but a large number of new histone retention sites were found only in the transgenerational generation DDT lineage sperm. Therefore, all three different epigenetic processes were concurrently altered as DDT induced the epigenetic tra...Continue Reading

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Datasets Mentioned

BETA
GSE109775
PRJNA430483
PRJNA430740

Methods Mentioned

BETA
sperm collection
immunoprecipitation
RNA-Seq
PCA
ChIP-Seq
acetylation
chips
Assay
PCR
chip

Software Mentioned

Tophat2
Cutadapt
Covaris
Bowtie2
in
MEDIPS R
Cufflinks
biomaRt R package
KEGG
DAVID

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