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Journal article
Tertiary Epimutations - A Novel Aspect of Epigenetic Transgenerational Inheritance Promoting Genome Instability
PloS one, Vol.11(12), pp.e0168038-e0168038
12/19/2016
PMCID: PMC5167269
PMID: 27992467
Abstract
Exposure to environmental factors can induce the epigenetic transgenerational inheritance of disease. Alterations to the epigenome termed "epimutations" include "primary epimutations" which are epigenetic alterations in the absence of genetic change and "secondary epimutations" which form following an initial genetic change. To determine if secondary epimutations contribute to transgenerational transmission of disease following in utero exposure to the endocrine disruptor vinclozolin, we exposed pregnant female rats carrying the lacI mutation-reporter transgene to vinclozolin and assessed the frequency of mutations in kidney tissue and sperm recovered from F1 and F3 generation progeny. Our results confirm that vinclozolin induces primary epimutations rather than secondary epimutations, but also suggest that some primary epimutations can predispose a subsequent accelerated accumulation of genetic mutations in F3 generation descendants that have the potential to contribute to transgenerational phenotypes. We therefore propose the existence of "tertiary epimutations" which are initial primary epimutations that promote genome instability leading to an accelerated accumulation of genetic mutations.
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Details
- Title
- Tertiary Epimutations - A Novel Aspect of Epigenetic Transgenerational Inheritance Promoting Genome Instability
- Creators
- John R McCarrey - The University of Texas at San AntonioJake D Lehle - The University of Texas at San AntonioSeetha S Raju - The University of Texas at San AntonioYufeng Wang - The University of Texas at San AntonioEric E Nilsson - Washington State UniversityMichael K Skinner - Washington State University
- Publication Details
- PloS one, Vol.11(12), pp.e0168038-e0168038
- Academic Unit
- Biological Sciences, School of
- Grant note
- SC1 GM100806 / NIGMS NIH HHS R01 ES012974 / NIEHS NIH HHS
- Identifiers
- 99901080306301842
- Language
- English
- Resource Type
- Journal article