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

Imprintome Definition Clarified

3 February 2017: 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.

There are a number of genes in the human genome that are expressed from only one copy or allele of the gene. The parental origin of some of these monoallelically expressed genes is random, like DGCR6 and DGCR6L (R. Das, 2010); however, others are expressed in a parent-of-origin dependent manner (Jirtle and Weidman 2007). The latter are called genomic imprinted genes, and are known to play critical roles in normal development, particularly in the brain. Since a single genomic mutation or epigenetic event can alter the normal function of these genes, it is necessary to define the repertoire of imprinted genes and their regulatory elements, the “imprintome.”

“Imprintome” first appeared in the scientific literature when I wrote a 2009 editorial for the premier issue of Epigenomics (Jirtle 2009). I further clarified its meaning in the paper, The Human Imprintome: Regulatory Mechanisms, Methods of Ascertainment, and Roles in Disease Susceptibility (Skaar et al. 2012). The “imprintome” is simply the complete set of environmentally labile imprint regulatory elements in the genome.

In other words, “imprintome" refers only to the differentially methylated regulatory (DMR) elements that control the parent-of-origin, monoallelic expression of genomic imprinted genes. It is NOT the repertoire of genes that are monoallelically expressed in a parental dependent manner, as suggested in TheScientist report.

As discussed in this article, there have been attempts to define imprinted genes in a number of animal and plant species, but so far, neither the “imprintome” nor the imprinted genes these regulatory elements control have been completely defined in any species. Nevertheless, in order to fully understand the genesis of diseases and disorders like autism, cancer, diabetes, obesity, and schizophrenia, this information will have to be determined for humans.

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...

Environmental Lead Exposure in Early Childhood Alters Imprinted Gene Regulation

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 in Environmental Health Perspectives, Cathrine Hoyo and her colleagues at North Carolina State University demonstrated, with the use of participants in the Cincinnati 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/IGF2 and PLAGL1/HYMAI - over three decades after exposure. Read more...

p16 Epimutation Causes Cancer

Hypermethylation of the promoter region of p16 causes cancer and reduces survival in mice according to a recent report by Lanlan Shen and her colleagues in The Journal of Clinical Investigation.

The history of p16 as a human tumor suppressor gene is complex. Only months after gene deletion evidence from a variety of tumor cell lines indicated the involvement of p16 in the genesis of cancer (Nobori et al. 1994; Kamb et al. 1994), its tumor suppressor function was brought into question (Spruck et al. 1994; Cairns et al. 1994).

According to the two-hit theory of carcinogenesis by Read more...

Antagonistic Growth Promoting Effects of Imprinted Genes

Imprinted genes are monoallelic expressed in a parent-of-origin dependent manner (Jirtle and Weidman 2007).The conflict theory of genomic imprinting predicts that maternally expressed genes are antigrowth while paternally expressed genes are progrowth (Haig and Graham 1991). The first two genes experimentally identified to be imprinted, the maternally expressed Igf2r (Barlow et al. 1991) and the paternally expressed Igf2 (DeChiara et al. 1991), were shown over two decades ago to adhere to this prediction. A second set of oppositely imprinted, fetal growth antagonistic genes has now been identified, the maternally expressed [Grb10](http://omim.org/entry/601523 Read more...