Integration of sperm ncRNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance
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Background: Environmentally induced epigenetic transgenerational inheritance of pathology and phenotypic variation has been demonstrated in all organisms investigated from plants to humans. This non-genetic form of inheritance is mediated through epigenetic alterations in the sperm and/or egg to subsequent generations. Although the combined regulation of differential DNA methylated regions (DMR), non-coding RNA (ncRNA), and differential histone retention (DHR) have been shown to occur, the integration of these different epigenetic processes remains to be elucidated. The current study was designed to examine the integration of the different epigenetic processes. Results: A rat model of transiently exposed F0 generation gestating females to the agricultural fungicide vinclozolin or pesticide DDT (dichloro-diphenyl-trichloroethane) was used to acquire the sperm from adult males in the subsequent F1 generation offspring, F2 generation grand offspring, and F3 generation great-grand offspring. The F1 generation sperm ncRNA had substantial overlap with the F1, F2 and F3 generation DMRs, suggesting a potential role for RNA-directed DNA methylation. The DMRs also had significant overlap with the DHRs, suggesting potential DNA methylation-directed histone retention. In addition, a high percentage of DMRs induced in the F1 generation sperm were maintained in subsequent generations. Conclusions: Many of the DMRs, ncRNA, and DHRs were colocalized to the same chromosomal location regions. Observations suggest an integration of DMRs, ncRNA, and DHRs in part involve RNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance.
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ncRNAs, due to their conspicuous amount and proportion in the transcriptome, play a central role in epigenetics with an incidence in all functional levels.
“Overall, ncRNAs, due to their conspicuous amount and proportion in the transcriptome, play a central role in epigenetics with an incidence in all functional levels (Figure 2).”
From Revisiting Epigenetics Fundamentals and Its Biomedical Implications (2024) · cites this paper as [80]
The Discussion (page not provided) suggests that sperm ncRNAs may help direct DNA methylation in epigenetic transgenerational inheritance, but says the study demonstrates correlations rather than validating that mechanism. It does not establish that ncRNAs occupy a conspicuous proportion of the transcriptome, that their abundance explains their role, or that they act at all functional levels. (LLM, conf=0.86)
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- Authors
- Beck, D., Ben Maamar, M., & Skinner, M. K.
- Affiliations
- Washington State University (US)
- Corresponding author
- Skinner, Michael K.
- ORCID
- Skinner, Michael K.
- Venue
- Epigenetics & Chromatin
- Published
- 2021-01-12
- Volume
- 14
- Issue
- 1
- Pages
- 6-6
- ISSN
- 1756-8935 (ISSN-L)
- PMC
- PMC7802319
- OpenAlex
- W3120639213
- Cited by
- 85
- References
- 48
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 18 · 2023: 16 · 2022: 19 · 2021: 8
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Epigenetics & Chromatin (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- John Templeton Foundation (50183, 61174)
- National Institutes of Health (ES012974)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- transgenerational epigenetic inheritance, DNA methylation, histone retention, RNA-directed DNA methylation, vinclozolin, DDT, pesticide exposure, environmental epigenetics, rat model
- MeSH terms
- Animals, Female, Histones, Male, Spermatozoa, Rats, Sprague-Dawley, DNA Methylation, RNA, Untranslated, Epigenesis, Genetic, Rats
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