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

William G. Kaelin, Jr. - Recipient of the 2019 Nobel Prize in Physiology or Medicine

7 October 2019: William G. Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza are this year's recipients of the Nobel Prize in Physiology or Medicine "... for their discoveries of how cells sense and adapt to oxygen availability."

When I joined the faculty at Duke University, I was investigating tumor oxygenation and blood flow regulation. At that time, third year Duke medical students were required to perform a research project. Bill Kaelin asked to do research in my lab in the early 1980s because of his early interest in tumor oxygenation. He demonstrated that the calcium antagonists verapamil and flunarizine significantly increased tumor blood flow, indicating their potential usefulness in improving cancer treatment with both chemotherapeutic agents and ionizing radiation.

Ultimately, his interest in the regulation of tissue oxygenation led to his seminal discovery that the von Hippel-Lindau tumor suppressor protein (pVHL) binds to the hypoxia-inducible factor (HIF) when a conserved proline residue is hydroxylated (Ivan et al, Science, 2001). This finding provided the first evidence that oxygen-induced modification of HIF plays a key mechanistic role in mammalian oxygen sensing, for which he won the Nobel Prize in Medicine.

Recent findings indicate that these intricate oxygen sensing pathways are not only changed through genetic mutations during disease formation, but can also be modified epigenetically (Dick et al, The Lancet, 2014; Pfeiffer et al, Sci Rep, 2016), bringing this area of research into the growing field of environmental epigenomics.

One of Bill Kaelin's undergraduate Duke University premed professors wrote when he was hoping to be become a physician researcher that "Mr. Kaelin appears to be a bright young man whose future lies outside of the laboratory." In contrast, I thought from the beginning that Bill had the intelligence, creativity, and drive required to be a pioneering research scientist. It is an honor to know Bill and to have had a small part to play in his scientific career. I am truly proud of him and his scientific contributions!

Jirtle Receives EMGS 2019 Alexander Hollaender Award

The Environmental Mutagenesis and Genomics Society (EMGS) Environmental Mutagenesis and Genomics Society (EMGS) honors its first president and Founder, Alexander Hollaender, by conferring the Hollaender Award annually in recognition of outstanding contributions in the application of the principles and techniques of environmental mutagenesis to the protection of human health.

This year, EMGS recognizes Dr. Jirtle's discovery that the environment can influence inheritance of phenotypic traits through epigenetic reprogramming representing one of the most important scientific advances of the 21st century. To quote his nominators: "His pioneering work in epigenetics and genomic imprinting has uncovered a vast territory in which a gene represents less of an inexorable sentence and more of an access point for the environment to modify the genome.&qu Read more...

Pioneer Scientists: Jack Fowler and Alfred Knudson

Sir Isaac Newton stated, "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) Fowler and Alfred George Knudson, Jr. Read more...

Imprintome Definition Clarified

Amber Dance published in TheScientist the 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...

Western Diet Blocks Gut Microbiome Programing of the Host Epigenome

Krautkramer et al. at the University of Wisconsin-Madison demonstrate 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 Jirtle prev Read more...

Imprinted Genes Implicated in the Puzzle of Autism

FOXG1 is potentially involved in the development of autism spectrum disorder (ASD). In a recent study, Dr. Vaccarino and 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 that FOXG1 overexpression, 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...