Tertiary Epimutations - A Novel Aspect of Epigenetic Transgenerational Inheritance Promoting Genome Instability
| Autor: | Eric E. Nilsson, Yufeng Wang, John R. McCarrey, Michael K. Skinner, Seetha S. Raju, Jake D. Lehle |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Genome instability Inheritance Patterns Gene Identification and Analysis lcsh:Medicine Endocrine Disruptors Kidney Biochemistry Epigenesis Genetic chemistry.chemical_compound Mutation Rate Genes Reporter Pregnancy Animal Cells Medicine and Health Sciences Vinclozolin lcsh:Science Oxazoles Genetics DNA methylation Multidisciplinary Spermatozoa Phenotype Chromatin Nucleic acids Phenotypes Female Epigenetics Cellular Types Anatomy DNA modification Chromatin modification Research Article Chromosome biology endocrine system Transgene Biology Genomic Instability 03 medical and health sciences Animals Point Mutation Mutation Detection Point mutation lcsh:R Biology and Life Sciences Kidneys Cell Biology Renal System DNA Epigenome Sperm Rats Germ Cells 030104 developmental biology chemistry Mutation lcsh:Q Gene expression |
| Zdroj: | PLoS ONE, Vol 11, Iss 12, p e0168038 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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