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

I had an Epiphany: Desire to Voluntarily Exercise May Be Epigenetically Determined in the Womb

24 January 2020: Should I go to the gym and exercise or sit on the couch and watch a movie? This is a question that we have all asked ourselves many times!

Robert Waterland and his research group at Baylor University have provided the first evidence that voluntary expenditure of energy, at least in mice, is determined in part by epigenetic changes established in early development (MacKay et al., Nat Commun, 2019).

This study showed that hypothalamic AgRP neuron-specific knockout of Dnmt3a leads to cell type-specific disruption of DNA methylation and the developmental upregulation of 1681 genes and downregulation of 2063 genes in these neurons, resulting in a decrease in voluntary exercise. Specifically, AgRP neuron-specific hypomethylation of the Bmp7 promoter increased its expression, causing widespread effects on TGFB signaling in the arcuate nucleus. These findings demonstrate a crucial role for DNA methylation in the normal development of the hypothalamic energy balance circuitry, and indicate that epigenetic mechanisms established early in life regulate an individual’s desire for physical activity.

Thus, choosing to go to the gym may be more difficult for some people than others not only because of social and genetic influences, but also because of epigenetic programming to reduce energy expenditure. This intriguing postulate may now also be investigated in humans since Waterland and his colleagues have recently defined a genomic atlas of related regions of systemic interindividual variation (CoRSIVs) that epigenetically control the expression of human metastable epialleles (Gunasekara et al., Genome Biol, 2019) - a novel subset of genes that is regulated epigenetically like the agouti gene in the Avy mouse (Waterland & Jirtle, Mol Cell Biol, 2003). The era of human environmental epigenomics and epidemiology is upon us.

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

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 le Read more...

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...