Transgenerational Epigenetic Inheritance TOP ARTICLES SUPPLEMENT CONTENTS EDITORIAL:: Epigenetics: where environment, society and genetics meet Epigenomics Vol. 6 Issue 1 REVIEW: Transgenerational epigenetic inheritance: adaption through the germline epigenome? Epigenomics Vol. 7 Issue 5 PERSPECTIVE: Transgenerational epigenetic inheritance: an open dicussion Epigenomics Vol. 7 Issue 5 Editorial Editorial Epigenetics: where environment, society and genetics meet “The goal is to use epigenetics to anticipate health in the individual and, more importantly, the population. Before this can be done, several challenges must be faced.” Keywords: environment • epigenetics • noncoding RNA • socioeconomic status • transgenerational epigenetic inheritance Understanding how environment, social fac- with environmental chemical exposure [3], tors and genetics combine to affect patterns race, gender [4] and income level [5]. How- of health is an urgent priority. Social factors ever, epigenetic gene regulation is bigger than that affect health patterns include race and methylation alone. socioeconomic status (SES), while biological Human and animal studies have begun factors include sex, genetics and epigenetics. to investigate environmental effects on epi- The consequence of biology and environ- genetics. While these publications are increas- ment can be observed in life expectancy ing, some factors need to be considered, these Amber V Majnik data. At 25 years old, life expectancy for include tissue specificity, epigenetic specific- Author for correspondence: white men is 4.4 years greater than for Afri- ity and transgenerational studies. Department of Pediatrics Medical can–American men. Females follow a similar College of Wisconsin, Milwaukee, pattern. Income also affects life expectancy Tissue specificity WI, USA with high income earners outliving their low Tissue-specific epigenetic profiles are well Tel.: +1 414 955 2374 [email protected] income counterparts, and white males and accepted, and so it must be noted that blood females outliving African–American males cells also have cell-specific profiles. Circulat- and females by 2–4 years at every income ing blood is a convenient source of material level [1] . Environment also affects perina- for epigenetic testing. It is minimally invasive tal mortality. US-born African–American to collect and can be collected multiple times women experience greater rates of perinatal over a period of time. However, develop- mortality than their foreign-born counter- ment and environment changes the cellular parts [2]. Similar patterns can be observed makeup of blood. with multiple health conditions, including Cellular heterogeneity may confound epi- cancer, depression, diabetes and heart disease genetic results, since epigenetics differs from highlighting the importance of this issue one blood cell to another [6,7]. For example, [1] . What is less clear is the mechanism by neutrophils predominate blood of a new- Robert H Lane which these disparities are caused. One way born, but, by 2–4 years, lymphocytes are Department of Pediatrics Medical in which biology and environment can both the majority population [8]. Furthermore, College of Wisconsin, Milwaukee, leave their fingerprint is through epigenetic cord blood also varies in its cellular make WI, USA changes. up compared to peripheral blood [9]. These Epigenetics refers to the regulation of gene two factors can confound the comparison of expression through modifications to DNA or methylation profiles from a newborn to an DNA-associated proteins. Epigenetic regula- adult, even in the same individual. The con- tion includes histone modifications, DNA stituents of the blood can also be changed if methylation and nonprotein coding RNA. the individual is experiencing inflammation, DNA methylation has been a particular focus an infection or high amounts of stress [10–12] . of environment-mediated changes in health. All of these factors can be influenced by an Methylation changes have been associated individual’s SES. These differences highlight part of 10.2217/EPI.13.83 © 2014 Future Medicine Ltd Epigenomics (2014) 6(1), 1–4 ISSN 1750-1911 1 Editorial Majnik & Lane how developmental and environmental changes can established effect of environment on epigenetics, envi- alter epigenetic results. ronmental factors such as those effecting SES could The importance of different epigenetic patterns disrupt this process. While the role for noncoding between specific cell types and whole blood will vary RNA is still being investigated, many studies have depending on disease or condition. Subtle differences begun to investigate how the environment can change are likely more important for multifactorial diseases, the life course of multiple generations and the role of like obesity, where the environment, genetics and social epigenetics in this process. factors all contribute to pathology. Furthermore, while methylation patterns may appear similar between cell Transgenerational epigenetic inheritance types, changes in histone code or noncoding RNA may One of the most challenging and intriguing aspects of differ. epigenetics is the transmission of modifications to sub- sequent generations. Transgenerational studies indicate Epigenetic specificity that epigenetic modifications are not wiped clean for We believe social and environmental factors rely on each generation, as was originally thought [16,17]. This, epigenetics to effect biologic change. The study of how transgenerational epigenetic inheritance, coupled with the environment affects phenotype is environmental the environmental influences of epigenetics indicates epigenetics. A cell has many epigenetic tools to modify that the environment of one generation can modify its gene expression in response to the environment. the phenotype of the following generations. This far- However, to understand environmental epigenetics, we reaching epigenetic effect indicates the importance of must look beyond gene expression and protein coding understanding environmental influences, such as SES, regions and pay attention to regulatory and noncod- on epigenetics. ing regions. This includes studying methylation and The life course approach determines how the social histone modifications, as well as noncoding RNA. and environmental context of one generation can The majority of SES studies give a limited view of affect another. For example, a maternal grandmother’s the epigenetic landscape. The majority of these stud- exposure to neighborhood poverty during pregnancy ies investigate SES and changes in global methylation. predicts the risk for infant low birth weight and sub- Some studies have taken an extra step to investigate sequent mortality among African–American women, methylation in disease relevant genes. However, to independent of the mother’s status [18]. A detailed fully appreciate the epigenetic impact of the environ- understanding of transgenerational epigenetics is nec- ment, analysis must go beyond methylation. Animal essary to understand this complex inheritance. models allow for a more detailed investigation of the epigenetic profile. Penaet al. analyzed DNA methyla- “The role for noncoding RNA in epigenetics tion and histone modifications of the estrogen recep- is just beginning to be understood; however, tor alpha gene in the brains of dams and pups in a a number of studies indicate that RNA could be a powerful player in transgenerational maternal care model [13] . These types of tissue specific, epigenetics. detailed epigenetic studies provide a more rigorous ” demonstration of epigenetic consequences. Stress is a core component of socioeconomic disad- While methylation is the best studied epigenetic vantage. Both prenatal as well as postnatal stress has mark, followed by histone modifications, the composi- been shown to effect long-term health. Epigenetic tion of our DNA is telling us that RNA may be much changes in offspring exposed to maternal stress have more important. The discovery that <3% of the human been noted in multiple species. In Drosophila, heat genome encodes protein-coding genes was surprising stress induces phosphorylation of the transcription fac- to many people. But perhaps what is more astounding tor dATF-2 [19] . This leads to a loss of heterochroma- is that scientists have now found that approximately tin structures at several region of the genome, which is 76% of the human DNA is transcribed into some sort transmitted to the next generation. In mice, the early of RNA [14] . Much of the 76% is thought to have a life stress of chronic unpredictable maternal separation regulatory role, including a role in epigenetics. leads to changes in behavior and alters the methylation The role for noncoding RNA in epigenetics is just profile in the promoter of candidate genes in the germ- beginning to be understood; however, a number of line and brain of affected males, as well as in the germ- studies indicate that RNA could be a powerful player line of the offspring [20]. The licking and grooming in transgenerational epigenetics. The role for RNA as a behavior of rats has also been shown to be associated mechanism of transfer of transgenerational phenotype with epigenetic changes and inherited [13] . come from experiments of microinjections of oliogri- Several additional aspects of SES have been modeled bonucleotides into egg and sperm cells [15] . Given the in studies of transgenerational epigenetic inheritance; 2 Epigenomics (2014) 11(1) future science group Epigenetics: where environment, society