Abstract
A variety of environmental toxicants and factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Epigenetic alterations in the germline (sperm or egg) are required to transmit transgenerational phenotypes. The current study was designed to investigate the potential role of histones in sperm to help mediate the epigenetic transgenerational inheritance. The agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to promote the epigenetic transgenerational inheritance of disease. Purified cauda epididymal sperm were collected from the transgenerational F3 generation control and exposure lineage male rats for histone analysis. A reproducible core of histone H3 retention sites was observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group of H3 retention sites plus additional differential histone retention sites (DHRs) were observed in the F3 generation exposure lineage sperm. Although new histone H3 retention sites were observed, negligible change in histone modification (methylation of H3K27me3) was observed between the control and exposure lineages. Observations demonstrate that in addition to alterations in sperm DNA methylation and ncRNA previously identified, the induction of differential histone retention sites (DHRs) also appear to be involved in environmentally induced epigenetic transgenerational inheritance.
Highlights
The initial epigenetic alteration in the transgenerational germline was found to be differential DNA methylation[2,5] and has been observed in a variety of species[6]
The current study used vinclozolin or DDT to induce the epigenetic transgenerational inheritance of disease in rats to investigate the potential that histone modifications or retention sites may be affected in the transgenerational rat sperm
The F3 generation males were aged to postnatal day 120 (P120) for cauda epididymal sperm collection
Summary
The initial epigenetic alteration in the transgenerational germline (sperm) was found to be differential DNA methylation[2,5] and has been observed in a variety of species[6]. The current study used vinclozolin or DDT to induce the epigenetic transgenerational inheritance of disease in rats to investigate the potential that histone modifications or retention sites may be affected in the transgenerational rat sperm. The core histone retention sites in the F3 generation control lineage were present and generally not altered in either the DDT or vinclozolin F3 generation lineage sperm, Fig. 1c.
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