Geneimprint
1 February 2013: Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. In this study, we show that LDIR significantly increases DNA methylation at the viable yellow agouti (Avy) locus in a dose- and sex-dependent manner. Moreover, maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring. Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide the first evidence that epigenetic alterations resulting from LDIR play a role in radiation hormesis (Calabrese and Baldwin 2002; Vincent Giuliano 2012), bringing into question the assumption that every dose of radiation is harmful. Since the epigenome varies markedly between species, the effect of LDIR on the epigenome in multiple generations needs to now be defined in humans. Epidemiological data alone will no longer suffice to assess our risk to low doses of ionizing radiation from environmental and clinical exposures.
Imprinted genes are monnoallelically expressed in a parent-of-origin dependent manner because the same parental allele is always epigenetically silenced (Jirtle and Weidman 2007). The phenomenon of genomic imprinting evolved in mammals around 200 million years ago in a common ancestor to marsupials and eutherians (Killian et al. 2000). Once this unique epigenetic form of gene regulation evolved, natural selection may have utilized the resulting marked variation in gene expression to drive mammalian speciation, providing a plausible explanation for why mammalian species vary markedly in their imprinted gene repertoires. Read more...
Not all multigenerational effects are transmitted through the germ line. Elegant studies in rats demonstrate that generation-to-generation attainment of the nurturing behaviors of pup licking and grooming and arch-back nursing are not germline inherited. Rather, they are passed on to the offspring directly from the mother during the first week of postnatal life through the induction of DNA methylation and histone alterations in the hippocampus (Weaver et al. 2004). Moreover, the inherent plasticity of the epigenome allows for the reversal of these modifications in adulthood by exposure to epigenetic therapeutic agents (Weaver et al. 2006). Read more...
Genomic imprinting is an epigenetic form of gene regulation that results in only the copy inherited from the mother or father to function. (Jirtle and Weidman 2007). The phenomenon of imprinting evolved about 150 M years ago in a common ancester to mammals that have live birth - the Therian mammals (Marsupials and Eutherians) (Killian et al. 2000). Read more...
The hypothesis of fetal origins of adult disease proposes that early developmental exposures involve epigenetic modifications, such as DNA methylation, that influence adult disease susceptibility (Jirtle and Skinner). In utero or neonatal exposure to bisphenol A (BPA), a high-production-volume chemical used in the manufacture of polycarbonate plastic, is associated with higher body weight, increased breast and prostate cancer, and altered reproductive function (Maffini et al.). Read more...
An epigenetic change alters the phenotype without changing the genotype. As a result of their unique genetic make-up, imprinted genes act as nodes of susceptibility for asthma, cancer, diabetes, obesity and many behavioral and developmental disorders - a list that is surprisingly long given the limited number of imprinted genes identified so far. The potential for malign influence at these sites is disproportionately large. In this respect, they're similar to the tyrannical pigs in George Orwell's Animal Farm, who famously declared, "all animals are equal, but some animals are more equal than others." The same is true for genes, and it's often the imprinted genes that are "more equal" in the formation of human diseases. Read more...
