Randy Jirtle Interview – Lucia Aronica

Jirtle delivers 2016 NCSU Commencement Address

– Jirtle interview by Nancy Barrand

– Destiny and DNA: Our Pliable Genome [Agouti Mouse Explained

– Epigenetics: How Genes and Environment Interact (Speaker: Randy Jirtle)

– Jirtle Interview on Epigenetics, 2010 [YouTube] [MP4]

Human imprinting disorders: Principles, practice, problems and progress

Do social insects support Haigs kin theory for the evolution of genomic imprinting?

Paternal Genome Elimination in Liposcelis Booklice (Insecta: Psocodea)

DNA methylation imprinting errors in spermatogenic cells from maturation arrest azoospermic patients

Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain

Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression

Characterizing the Imprintome: Three Techniques for Identifying the Collection of Maternal and Paternal Genes Silenced in Offspring

Monoallelic Gene Expression in Mammals

Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues

Epigenomic engineering for Down syndrome

Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes

Epigenomics meets splicing through the TETs and CTCF

Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time

Genetic sources of population epigenomic variation

Visualizing allele-specific expression in single cells reveals epigenetic mosaicism in an H19 loss-of-imprinting mutant

FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders

Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain

Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

Omics and endocrine-disrupting chemicals – new paths forward

Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism

Epigenetic regulation of miR-200 as the potential strategy for the therapy against triple-negative breast cancer

NLRPs, the subcortical maternal complex and genomic imprinting

Welcome to the 10th volume of Epigenomics

CCR6 promotes steady-state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance

Whole Genome DNA Methylation Analysis Using Next-Generation Sequencing (BS-seq)

Convergence between biological, behavioural and genetic determinants of obesity

Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration

Variant calling from RNA-seq data of the brain transcriptome of pigs and its application for allele-specific expression and imprinting analysis

JAK2V617F influences epigenomic changes in myeloproliferative neoplasms

Utilizing biomarkers in colorectal cancer: an interview with Ajay Goel

Recent trends on the role of epigenomics, metabolomics and noncoding RNAs in rationalizing mood stabilizing treatment

Genetic determinants of low birth weight

The IBD interactome: an integrated view of aetiology, pathogenesis and therapy

Denise Barlow (1950-2017)-pioneer of genomic imprinting

Parental-genome dosage effects on the transcriptome of F1 hybrid triploid embryos of Arabidopsis thaliana

Naive pluripotent stem cells as a model for studying human developmental epigenomics: opportunities and limitations

Epigenetics: The Future Direction in Systemic Sclerosis

Hot off the press is a daily listing of the most recent articles in epigenetics and imprinting

Pioneer Scientists: Jack Fowler and Alfred Knudson

Fowler.Phys Med Biol51:R263-86 (2006)

Other Articles:Knudson. Annu Rev Genomics Hum Genet. 2005;6:1-14.

21 March 2017:Sir Isaac Newtonstated, If I have seen further, it is by standing on the shoulders of giants.” Two prominent scientists who significantly altered my scientific career died this past year –John Francis (Jack) FowlerandAlfred George Knudson, Jr.

I received my BS in 1970 from theUniversity of Wisconsin (UW)inNuclear Engineering. I transitioned from the physical to the biological sciences as a graduate student at the UW under the mentorship ofKelly Hardenbrook Clifton. My shift from nuclear engineering to a radiobiology was assisted greatly by Jack Fowler’s pioneering research in tumor oxygenation and the mathematical modeling of the interaction of radiation with normal and malignant tissues during fractionated radiation therapy. Later when I was atDuke University, I invited Dr. Fowler to give anAlpha/Beta Model Workshopand aLecture on Radiation Fractionationto describe how to maximize the therapeutic effects of radiation in the treatment of cancer.

Alfred Knudson, a physician and cancer geneticist, is widely known for histwo-hit hypothesisto explain the incidence of hereditary and nonhereditary forms of retinoblastomas (Knudson PNAS 68: 820-823, 1971). This innovative conceptual framework on how to view the genesis of cancer ultimately led to the identification of the retinoblastoma tumor suppressor gene,RB1(Friendet al.Nature 223: 643-646, 1986).

Our lab subsequently used the Knudson two-hit hypothesis of tumorigenesis to provide the first evidence that theInsulin like Growth Factor 2 Receptor (IGF2R)also functions as a tumor suppressor (De Souzaet al.Nat. Genet.). SinceIGF2Ris imprinted (i.e. one copy of the gene silenced by DNA methylation), this finding thrusted me into the rapidly growing research field ofepigenetics. Interestingly, I had the honor of finally meeting Dr. Knudson almost a decade later in Stockholm, Sweden at the 2004 Nobel Symposium on epigenetics entitled,Epigenetic Reprogramming in Development and Disease. I will greatly miss these pioneering scientists upon whose shoulders I stood.

Amber Dancepublished inTheScientistthe paper,Characterizing the Imprintome: Three Techniques for Identifying the Collection of Maternal and Paternal Genes Silenced in Offspring.

Although it is important to inform people that scientists are attempting to define this subset of genes in a number of species, “imprintome” is not used in this paper as it was originally intended. The word “imprintome” needs to be used in the precise way we initially defined it so confusion is not introduced into a scientific subject that is already difficult to understand.Read more…

Krautkrameret theUniversity of Wisconsin-Madisondemonstrate in this study that the gut microbiome regulates global histone acetylation and methylation not only in the colon, but also in tissues outside the gut (i.e. liver and fat). Moreover, consumption of a ‘‘Western-type’’ diet prevents many of the microbiota-dependent chromatin changes that occur in a polysaccharide-rich diet by limiting the formation of microbial short-chain fatty acids (SCFA). These findings suggest the intriguing possibility that gut microbiome-mediated alterations in the host epigenome may be mechanistically involved in the genesis of chronic diseases, such as cardiovascular disease, obesity, diabetes, inflammatory bowel disorders, and cancer.Waterland and JirtleprevRead more…

FOXG1is potentially involved in the development of autism spectrum disorder (ASD). In a recent study,Dr. Vaccarinoand her colleagues at Yale University used a novel 3D organoid culture of human neural cells that were derived from induced pluripotent stem cells (iPSCs) obtained from the skin cells of people with and without severe idiopathic ASD. This study provides evidence thatFOXG1overexpression, rather than gene mutation, induces a GABAergic neuron fate that functions as a developmental precursor to ASD.DLGAP2, the other gene listed in the accompanying graphic, has also been implicated in the development of autism in a copy number
variation(CNV)analysis of people with ASD.Read more…

Although lead (Pb) is a neurotoxin, the mechanism by which it effects neurodevelopment, and the acceptable threshold of exposure to the developing child are still unclear. Imprinted genes have one parental allele silenced epigenetically, and they play critical roles in human development (Jirtle and Weidman 2007). In a recent study published inEnvironmental Health Perspectives,Cathrine Hoyo and her colleagues at North Carolina State University demonstrated, with the use of participants in theCincinnati Lead Study, that children exposed early in development to high levels of Pb have altered DNA methylation in the regulatory elements of imprinted genes -PEG3, H19/IGF2andPLAGL1/HYMAI- over three decades after exposure.Read more…

Hypermethylation of the promoter region ofp16causes cancer and reduces survival in mice according to a recent report byLanlan Shenand her colleagues inThe Journal of Clinical Investigation.

The history ofp16as a human tumor suppressor gene is complex. Only months after gene deletion evidence from a variety of tumor cell lines indicated the involvement ofp16in the genesis of cancer (Noboriet al.1994Kambet al.1994), its tumor suppressor function was brought into question (Sprucket al.1994Cairnset al.1994).

According to the two-hit theory of carcinogenesis byRead more…