Animal models of epigenetic inheritance.
ABSTRACT Although genomic DNA is the template of our heredity, it is the coordination and regulation of its expression that results in the wide complexity and diversity seen among organisms. In recent years, an emerging body of evidence has focused on the role of epigenetics as one mechanism by which gene expression can be maintained and modulated throughout the lifetime of an individual. Epigenetics refers to heritable alterations in gene expression that are not mediated by changes in primary DNA sequence and includes mitotic and/or meiotic events. In essence, epigenetic modulation results in functional adaptations of the genomic response to the environment and is believed to play a fundamental role in early developmental plasticity. This article focuses on several animal models that have been developed over the past decade to study epigenetic inheritance, many of which have arisen from the developmental origins of adult health and disease fields.
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ABSTRACT: Transcriptional co-activators, co-repressors and chromatin remodeling machines are essential elements in the transcriptional programs directed by the master adipogenic transcription factor PPARgamma. Many of these components have orthologs in other organisms, where they play roles in development and pattern formation, suggesting new links between cell fate decision-making and adipogenesis. This review focuses on bromodomain-containing protein complexes recently shown to play a critical role in adipogenesis. Deeper understanding of these pathways is likely to have major impact on treatment of obesity-associated diseases, including metabolic syndrome, cardiovascular disease and Type 2 diabetes. The research effort is urgent because the obesity epidemic is serious; the medical community is ill prepared to cope with the anticipated excess morbidity and mortality associated with diet-induced obesity.FEBS letters 08/2010; 584(15):3260-8. DOI:10.1016/j.febslet.2010.05.030 · 3.34 Impact Factor
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ABSTRACT: While many fetuses are exposed to tobacco in utero, not all experience adverse outcomes as a result of this exposure. Mechanisms leading to the attenuation of fetal birth weight and adverse pregnancy outcomes are complex. Therefore many studies have begun to focus, not only on the contribution of maternal and fetal genes to phenotypic outcome, but also on epigenetic changes associated with exposure to maternal tobacco smoke. In this review, we detail the epidemiologic evidence associating an adverse pregnancy outcome to maternal tobacco use. We provide a brief summary of studies demonstrating an association between maternal and fetal gene polymorphisms with low birth weight in response to maternal tobacco exposure. We also review the literature showing epigenetic changes in the offspring associated with in utero tobacco exposure. The complex interplay of genomic and epigenomic factors may contribute to specific phenotypic outcomes and can help begin to elucidate the differential susceptibilities to tobacco smoke in utero.Pediatric endocrinology reviews: PER 12/2010; 8(2):94-102.
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ABSTRACT: Intraspecific phenotypic variation (PV) in deer is common, at times impressively diverse, and involves morphology, development, physiology, and behaviour. Until recently considered a nuisance in evolutionary and taxonomic studies, PV has become the primary target to study fossil and extant species. Phenotypes are traditionally interpreted to express primarily interactions of inherited genetic variants. PV certainly originates from different genotypes, but additional PV, referred to as phenotypic plasticity (PP), results from gene expression responsive to environmental conditions and other epigenetic factors. Usage of ‘epigenetics’ for PP has increased exponentially with 20 316 published papers (Web-of-Science 1990 – May 2010), yet it does not include a single paper on cervids (1900 to the present). During the ‘genomic era’, the focus was on the primaryDNAsequences and variability therein. Recently however, several higher order architectural genomic features were detected which all affect PV. (1) Genes: poli-genic traits; pleiotropic genes; poli-allelic genes; gene dosage (copy number variants, CNV); single nucleotide variance in coding and gene regulatory regions; mtDNA recombinations and paternal mtDNA inheritance. (2) Gene products: pleiotropic gene products; multiple protein structures through alternative splicing; variable gene product reactions due to gene dosage. (3) Gene expression: (i) epigenetic regulation at the DNA, nucleosomal and chromosomal levels; (ii) large-scale genomic structural variation (i.e. CNV imbalance); (iii) transcription factor proteins (TF), each regulating up to 500 target genes, with TF activity varying 7.5–25% among individual humans (exceeding variation in coding DNA by 300–1000·); (iv) non-protein-coding RNA (98.5% of genome) constituting maybe hundreds of thousands RNA signals; (v) gene expression responsive to external and internal environmental variation; (vi) transgenerational epigenetic inheritance (e.g. from ubiquitous non-gametic interactions, genomic imprinting, epistasis, transgenerational gene–diet interactions); (vii) epigenetic stochasticity resulting in random PP. A unique example of labile traits in mammals is the yearly regrowth of a complete appendage, the antler in cervids. Highly complex assortments of genotypes lead to a spectrum of phenotypes, yet the same spectrum can result if a single genotype generates highly complex assortments of epigenotypes. AlthoughDNAis the template for theDNA–RNA–protein paradigm of heredity, it is the coordination and regulation of gene expression that results in wide complexity and diversity seen among individual deer, and per-generation variety of phenotypes available for selection are greater than available genotypes. In conclusion, epigenetic processes have fundamental influences on the great intraspecific PV found in deer, which is reflected in broad ranges of environmental conditions under which they can persist. Deer management and conservation of endangered cervids will benefit from appreciating the large inherent PV among individuals and the immense contribution of epigenetics in all aspects of deer biology and ecology.Animal Production Science 01/2011; 51(4):365-374. DOI:10.1071/AN10169 · 1.03 Impact Factor