http://www.geneimprint.com/ Recent articles of special importance in the field of genomic imprinting. en-us Sat, 14 Mar 2026 23:53:31 EDT Sat, 14 Mar 2026 23:53:31 EDT jirtle@radonc.duke.edu james001@jirtle.com Jima DD, Skaar DA, Planchart A, Motsinger-Reif A, Cevik SE, Park SS, Cowley M, Wright F, House J, Liu A, Jirtle RL, Hoyo C
Epigenetics (Jul 2022)

Imprinted genes - critical for growth, metabolism, and neuronal function - are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.]]> Wed, 31 Dec 1969 19:00:00 EST Skaar DA, Dietze EC, Alva-Ornelas JA, Ann D, Schones DE, Hyslop T, Sistrunk C, Zalles C, Ambrose A, Kennedy K, Idassi O, Miranda Carboni G, Gould MN, Jirtle RL, Seewaldt VL
Cancers (Basel) (Nov 2021)

Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, gene amplification accounts for increased expression in <10% of these breast cancers. Here, we showed that is imprinted in breast tissue and identified a differentially methylated region (DMR) controlling its imprint status. Hypomethylation at the DMR, coupled with biallelic expression of , occurred in 63% of triple-negative breast cancers (TNBC). The association between hypomethylation and TNBC status was highly significant in African-Americans ( = 0.006), but not in Caucasians ( = 0.70). hypomethylation was also found in non-cancerous tissue from 77% of women at high-risk of developing breast cancer. Functional studies demonstrated that the gene product, TASK3, regulates mitochondrial membrane potential and apoptosis-sensitivity. In TNBC cells and non-cancerous mammary epithelial cells from high-risk women, hypomethylation of the DMR predicts for increased TASK3 expression and mitochondrial membrane potential ( < 0.001). This is the first identification of the DMR in mammary epithelial cells and demonstration that its hypomethylation in breast cancer is associated with increases in both mitochondrial membrane potential and apoptosis resistance. The high frequency of hypomethylation of the DMR in TNBC and non-cancerous breast tissue from high-risk women provides evidence that hypomethylation of the DMR/TASK3 overexpression may serve as a marker of risk and a target for prevention of TNBC, particularly in African American women.]]> Wed, 31 Dec 1969 19:00:00 EST Skaar DA, Li Y, Bernal AJ, Hoyo C, Murphy SK, Jirtle RL
ILAR J (Jan 2012)

Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin-dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.]]> Wed, 31 Dec 1969 19:00:00 EST Waterland RA, Jirtle RL
Mol Cell Biol (Aug 2003)

Early nutrition affects adult metabolism in humans and other mammals, potentially via persistent alterations in DNA methylation. With viable yellow agouti (A(vy)) mice, which harbor a transposable element in the agouti gene, we tested the hypothesis that the metastable methylation status of specific transposable element insertion sites renders them epigenetically labile to early methyl donor nutrition. Our results show that dietary methyl supplementation of a/a dams with extra folic acid, vitamin B(12), choline, and betaine alter the phenotype of their A(vy)/a offspring via increased CpG methylation at the A(vy) locus and that the epigenetic metastability which confers this lability is due to the A(vy) transposable element. These findings suggest that dietary supplementation, long presumed to be purely beneficial, may have unintended deleterious influences on the establishment of epigenetic gene regulation in humans.]]> Wed, 31 Dec 1969 19:00:00 EST Jirtle RL
Epigenomics (Jan 2022)

In this interview, Professor Randy L Jirtle speaks with Storm Johnson, Commissioning Editor for , on his work on genomic imprinting, environmental epigenomics and the fetal origins of disease susceptibility. Professor Randy Jirtle joined the Duke University Department of Radiology in 1977 and headed the Epigenetics and Imprinting Laboratory until 2012. He is now Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC, USA. Jirtle's research interests are in epigenetics, genomic imprinting and the fetal origins of disease susceptibility. He is known for his groundbreaking studies linking environmental exposures early in life to the development of adult diseases through changes in the epigenome and for determining the evolutionary origin of genomic imprinting in mammals. He has published over 200 peer-reviewed articles as well as the books  and  . He was honored in 2006 with the Distinguished Achievement Award from the College of Engineering at the University of Wisconsin-Madison. In 2007, he was a featured scientist on the television program on epigenetics titled 'Ghost in Your Genes' and was nominated for Time Magazine's 'Person of the Year'. He was the inaugural recipient of the Epigenetic Medicine Award in 2008 and received the STARS Lecture Award in Nutrition and Cancer from the National Cancer Institute in 2009. Jirtle was presented the Linus Pauling Award from the Institute of Functional Medicine in 2014. In 2017, ShortCutsTV produced the English documentary 'Are You What Your Mother Ate? The Agouti Mouse Study' based on his pioneering epigenetic research. He received the 2018 Northern Communities Health Foundation Visiting Professorship Award at the University of Adelaide, Australia. The Personalized Lifestyle Medicine Institute presented Jirtle with the Research and Innovation Leadership Award in 2019. Dr Jirtle was also given the Alexander Hollaender Award in 2019 at the 50th annual meeting of the Environmental Mutagenesis and Genomics Society.]]> Wed, 31 Dec 1969 19:00:00 EST Svoboda LK, Perera BPU, Morgan RK, Polemi KM, Pan J, Dolinoy DC
Chem Res Toxicol (Aug 2022)

The rapidly growing field of toxicoepigenetics seeks to understand how toxicant exposures interact with the epigenome to influence disease risk. Toxicoepigenetics is a promising field of environmental health research, as integrating epigenetics into the field of toxicology will enable a more thorough evaluation of toxicant-induced disease mechanisms as well as the elucidation of the role of the epigenome as a biomarker of exposure and disease and possible mediator of exposure effects. Likewise, toxicoepigenetics will enhance our knowledge of how environmental exposures, lifestyle factors, and diet interact to influence health. Ultimately, an understanding of how the environment impacts the epigenome to cause disease may inform risk assessment, permit noninvasive biomonitoring, and provide potential opportunities for therapeutic intervention. However, the translation of research from this exciting field into benefits for human and animal health presents several challenges and opportunities. Here, we describe four significant areas in which we see opportunity to transform the field and improve human health by reducing the disease burden caused by environmental exposures. These include (1) research into the mechanistic role for epigenetic change in environment-induced disease, (2) understanding key factors influencing vulnerability to the adverse effects of environmental exposures, (3) identifying appropriate biomarkers of environmental exposures and their associated diseases, and (4) determining whether the adverse effects of environment on the epigenome and human health are reversible through pharmacologic, dietary, or behavioral interventions. We then highlight several initiatives currently underway to address these challenges.]]> Wed, 31 Dec 1969 19:00:00 EST Jirtle RL
Essays Biochem (Jul 2025)

Two epigenetically labile subsets of genes that link embryonic environmental exposures with adult disease susceptibility are those that are imprinted and those with metastable epialleles. The expression of genes with metastable epialleles, like the agouti gene in Agouti viable yellow (Avy) mice, is highly variable between individuals but uniform in tissues within an individual. We used the Avy mouse to demonstrate that exposure to nutritional supplements, chemical toxicants, and low-dose ionizing radiation during embryogenesis alters adult disease susceptibility by modifying the epigenome. Genomic imprinting is a unique species-dependent epigenetic form of gene regulation that evolved approximately 150 million years ago in a common ancestor to Therian mammals. It resulted in monoallelic parent-of-origin-dependent gene silencing. Thus, imprinted genes are functionally haploid disease susceptibility loci, since only a single genetic or epigenetic event is required to alter their function. Expression of imprinted genes in the human genome is regulated by hemi-methylated imprint control regions (ICRs) in the human imprintome. Furthermore, human imprintome ICRs associated with chronic diseases (e.g., cancer, diabetes, and obesity) and behavioral disorders (e.g., autism, bipolar disorder, psychopathy, and schizophrenia) can now be identified with the use of cells from peripheral samples and the human imprintome array. The importance of metastable epialleles and imprinted genes in the etiology of environmentally induced human chronic diseases is discussed in this review.]]> Wed, 31 Dec 1969 19:00:00 EST Carreras-Gallo N, Dwaraka VB, Jima DD, Skaar DA, Mendez TL, Planchart A, Zhou W, Jirtle RL, Smith R, Hoyo C
bioRxiv (Jan 2024)

Differentially methylated imprint control regions (ICRs) regulate the monoallelic expression of imprinted genes. Their epigenetic dysregulation by environmental exposures throughout life results in the formation of common chronic diseases. Unfortunately, existing Infinium methylation arrays lack the ability to profile these regions adequately. Whole genome bisulfite sequencing (WGBS) is the unique method able to profile these regions, but it is very expensive and it requires not only a high coverage but it is also computationally intensive to assess those regions.]]> Wed, 31 Dec 1969 19:00:00 EST Cevik SE, Skaar DA, Jima DD, Liu AJ, Whitson HE, Jirtle RL, Hoyo C, Planchart A
Clin Epigenetics (Apr 2024)

Alzheimer's disease (AD) prevalence is twice as high in non-Hispanic Blacks (NHBs) as in non-Hispanic Whites (NHWs). The objective of this study was to determine whether aberrant methylation at imprint control regions (ICRs) is associated with AD. Differentially methylated regions (DMRs) were bioinformatically identified from whole-genome bisulfite sequenced DNA derived from brain tissue of 9 AD (5 NHBs and 4 NHWs) and 8 controls (4 NHBs and 4 NHWs). We identified DMRs located within 120 regions defined as candidate ICRs in the human imprintome ( https://genome.ucsc.edu/s/imprintome/hg38.AD.Brain_track ). Eighty-one ICRs were differentially methylated in NHB-AD, and 27 ICRs were differentially methylated in NHW-AD, with two regions common to both populations that are proximal to the inflammasome gene, NLRP1, and a known imprinted gene, MEST/MESTIT1. These findings indicate that early developmental alterations in DNA methylation of regions regulating genomic imprinting may contribute to AD risk and that this epigenetic risk differs between NHBs and NHWs.]]> Wed, 31 Dec 1969 19:00:00 EST Jirtle RL
Environ Epigenet (Jan 2025)

Genomic imprinting is a phenomenon in which one parental allele is silenced epigenetically. My research has focused on the role of epigenetics in human health and disease since 1995 when we identified the first tumor suppressor gene that is also imprinted, the . Subsequently, by using the agouti viable yellow (A) mouse model, we demonstrated that increased maternal dietary exposure to methyl donors altered offspring phenotype in adulthood by modifying the epigenome, providing a plausible mechanism for the developmental origins of health and disease (DOHaD). Consequently, the field of epigenetics can be thought of as the "science of hope," since personal changes in diet and physical activity can potentially alter the epigenome to prevent chronic disease formation, and potentially, even ameliorate the negative effects of environmental exposures to chemical and physical toxicants. In this perspectives article, I address a series of questions posed about the field of environmental epigenetics, and discuss the role that the environmentally labile -acting, imprint regulatory elements in the human genome (i.e. the human imprintome) and the correlated regions of systemic interindividual variation (CoRSIVs) play in disease formation and behavioral development.]]> Wed, 31 Dec 1969 19:00:00 EST