Geneimprint
28 December 2025: At the turn of the millennium, three epigenetic papers were particularly instrumental in ushering in the era of environmental epigenomics (Jirtle, 2025). Firstly, in 2003, the agouti mouse study demonstrated that maternal dietary methyl supplementation (i.e. folic acid, vitamin B12, choline, and betaine) significantly increased the number of healthy, brown offspring by altering the epigenome at the Avy locus (Waterland and Jirtle, 2003). This finding provided a plausible mechanism to explain how environmental exposures during embryonic development could alter disease susceptibility in adulthood. Secondly, in 2004, postnatal maternal licking and grooming behavior in rats was shown to produce in the offspring stable DNA methylation and chromatin structure alterations in the promoter of the glucocorticoid receptor, Nr3c1, in the hippocampus of the brain (Weaver et al., 2004). This provided a mechanism for the long-term effects of postnatal maternal care on gene expression and behavior in the offspring. Thirdly, in 2005, evidence was provided that the endocrine-disrupting agents, vinclozolin and methoxychlor, induce transgenerationally inherited alterations that lead to decreased male fertility and spermatogenic capacity by reprogramming the male germ line epigenetically (Anway et al., 2005).
Because of these pioneering studies two decades ago, the era of 'environmental epigenomics' was ushered into the consciousness of both scientists and the general public. The first meeting on this research subject was at a joint NIEHS/Duke University conference that Fred Tyson and I co-organized at the Washington Duke Inn in Durham, NC in November of 2005, making this year the twentieth anniversary of the 'Woodstock' gathering for this field of research.
With the subsequent identification of the imprint control regions (ICRs) that regulate the expression of imprinted genes - the human imprintome (Jima et al., 2022 and Jirtle, 2025) and the correlated regions of systemic interindividual variations (CoRSIVs) (Gunasekara et al., 2019), the development of the human imprintome array (Carreras-Gallo et al., 2024), and the ability to now perform superior high-throughput DNA methylation sequencing, as Winston Churchill stated, we are at the 'end of the beginning' of the era of environmental epigenetics research.
In the future, we should literally be able to readily determine the importance of ICRs and CoRSIVs in the pathogenesis of all chronic diseases and behavioral disorders that plague humans. Moreover, we may be able to ameliorate some of these negative health effects through the modification of our diet (Aronica et al. 2025).
Francis Crick, James Watson, and Maurice Wilkins won the 1962 Nobel Prize in Physiology or Medicine for their discovery of the double-helix structure of DNA. Sadly, the last of these Nobel laureates, James D. Watson, died November 6, 2025 in East Northport, New York at the age of 97 (AACR Memoriam). Read more...
The monoallelic parent-of-origin dependent expression of imprinted genes is regulated by differentially methylated imprint control regions (ICRs) - the human imprintome. The epigenetic dysregulation of the imprintome by environmental exposures during early development results in the fetal origins of behavioral disorders and common chronic diseases. Whole genome bisulfite sequencing (WGBS) is a unique method to profile these ICRs (Cevik, et. al. 2024); however, it is computationally intensive since it requires high coverage, making it expense for use in large epidemiological studies. Read more...
Using WGBS and the recently identified human imprintome (Jima et al., 2022), we provide the first evidence that DNA methylation in 120 candidate imprint control regions (ICRs) varies markedly in the brains of people with Alzheimer's disease (AD) versus that in controls (Cevik et al., 2024). Read more...
In 1953 Watson and Crick determined the structure of DNA. Fifty years later Waterland and Jirtle demonstrated with the Agouti Mouse Study that the fetal origins of adult disease susceptibility results from alterations in the epigenome - the genetic programs that tell the genes when, where and how to work. Thus, not only mutations in the genome, but also changes in the epigenome function in the genesis of human health and disease. Read more...
Genomic imprinting is a unique epigenetic form of gene regulation that evolved in marsupials and placental mammals about 150 million years ago (Imprinting Evolution in Mammals). It results in only one copy of a gene being expressed in a parent-of-origin dependent manner. Thus, imprinted genes are disease susceptibility loci since a single genetic or epigenetic event can alter their function.
Imprinted genes are heavily involved in metabolism and growth regulation. An epigenetic tug-of-war between the mothers and fathers imprinted genes during development has been postulated to explain variations in the fetal origins of metabolic disorders such as obesity and type 2 diabetes, as well as cancer, and a spectrum of mental disorders ranging from autism to schizophrenia (Badcock and Crespi, 2008). Read more...
