Epigenetics in congenital diseases and pervasive developmental disorders

Kubota T.
Environ Health Prev Med. 2008 Jan;13(1):3-7. Epub 2007 Dec 11.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698247/pdf/12199_2007_Article_8.pdf

Epigenetics is an intrinsic mechanism that alters gene function - not by altering DNA sequences, but by chemically modifying the DNA and chromosomal histone proteins. Epigenetics is involved in genomic imprinting and X-chromosome inactivation in humans, and the failure of this mechanism causes a subset of congenital syndromes and cancers. Until recently, it has been believed that epigenetic modification is stable and that the pattern is faithfully preserved following DNA replication during cell division, leading to stable epigenomic patterns during one's life-time. However, more recent reports of environmental stress altering the epigenomic patterns within a short time frame after birth, followed by alterations in gene expression and phenotype, indicate that epigenetics is not only involved in congenital neurodevelopmental diseases but also in acquired diseases, including pervasive developmental disorders, through gene-environmental interaction. In this review, I introduce the subject of congenital diseases with abnormalities in known epigenetic mechanisms and discuss possible epigenetic abnormalities in pervasive developmental disorders.

Environmental influences on epigenetic profiles.
Suter MA, Aagaard-Tillery KM.
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Semin Reprod Med. 2009 Sep;27(5):380-90. Epub 2009 Aug 26.
http://www.thieme-connect.com/DOI/DOI?10.1055/s-0029-1237426

Studies of environmental challenges, such as hazardous air pollutants, nonmutagenic toxins, diet choice, and maternal behavioral patterns, reveal changes in gene expression patterns, DNA methylation, and histone modifications that are in causal association with exogenous exposures. In this article we summarize some of the recent advances in the field of environmental epigenetics and highlight seminal studies that implicate in utero exposures as causative agents in altering not only the epigenome of the exposed gestation, but that of subsequent generations. Current studies of the effects of maternal behavior, exposure to environmental toxins, and exposure to maternal diet and an altered gestational milieu are summarized.

Epigenetics and environmental chemicals.
Baccarelli A, Bollati V.
Laboratory of Environmental Epigenetics, Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, University of Milan, Via San Barnaba 8, Milan, Italy. andrea.baccarelli@unimi.it
Curr Opin Pediatr. 2009 Apr;21(2):243-51.
http://journals.lww.com/co-pediatrics/Abstract/2009/04000/Epigenetics_and_environmental_chemicals.14.aspx

PURPOSE OF REVIEW: Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals. RECENT FINDINGS: In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, and methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, and TCA), air pollutants (particulate matter, black carbon, and benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, and dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modifications and microRNA. SUMMARY: For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed individuals develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally.