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

Imprinted Genes Implicated in the Puzzle of Autism

28 July 2015: 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. Interestingly, there is strong evidence that both of these genes are imprinted and expressed from the paternal allele (Luedi et al. 2007), as predicted by Christopher Badcock and Bernard Crespi in their imprinted brain theory.

Imprinted genes are monoallelically expressed in a parent-of-origin dependent manner. Since the nonfunctional copy is silenced epigenetically, environmental factors that alter the epigenome can result in what is called loss of imprinting (LOI). This results in imprinted genes being either hypo or hyper expressed because of alterations in the epigenome (e.g. DNA methylation) rather than mutations in the genome. To determine the overall role of imprinting in the puzzle of ASD requires the identification of the complete repertoire of human imprinted genes and their regulatory elements - The Imprintome. Although this information is presently not available, it is crucial to determine now if the expression of FOXG1 and/or DLGAP2 are epigenetically dysregulated in ASD.

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...

Autism and Schizophrenia: The Antithesis of Each Other?

Genomic imprinting is a phenomenon where one parental allele is silenced epigenetically, resulting in monoallelic parent-of-origin gene expression (Jirtle and Weidman 2007). It evolved about 150 million years ago with the advent of viviparity and placentation in a common ancestor to Therian mammals (i.e. Marsupials and Eutherians) (Killian et al. 2000). Badcock and Crespi postulated in their imprinted brain theory that autism spectrum disorders (AS) and schizophrenia spectrum (SS) disorders are the antithesis of each other, and result from the skewing of paternally and maternally imprinted gene expression in the brain during development. Paternally expressed imprinted genes tend to be progrowth, and those that are maternally expressed antigrowth. Read more...

Environmental Epigenomics in Health and Disease

Springer has recently published two books on environmental epigenomics that are edited by Randy L. Jirtle and Frederick L. Tyson -- Epigenetics and Disease Origins and Epigenetics and Complex Diseases. The overall purpose of these books is to give readers an overview of how environmental exposures can influence the risk of disease in adulthood by disrupting epigenetic processes and reprogramming during early development. Read more...