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• W2139790010 abstract "In modern biology, Mendelian genetics provides a magnificent framework to deal with the causal relationship between genetic mutations and biological phenotypes, thus greatly promoting our understanding of developmental process of plants and animals. By analysing such mutants, as well as the etiology of human genetic diseases, we can identify the responsible genes. This type of thinking provided strong arguments for the human genome project, starting in the 1990s following several genome projects of other simpler organisms. The genome comprises all the genes in the organism and is a blueprint controlling development, growth and behaviour.That is why discovery of genomic imprinting in 1984 had such a great impact on modern biology. It is a clear exception to the simple Mendelian genetics described earlier and demonstrated that epigenetic mechanisms also play essential roles in the mammalian developmental systems. Several exceptions to Mendelian rules had already been reported in plants and insects. Genomic imprinting is an epigenetic mechanism regulating parental origin-specific gene regulation of certain subsets of genes, called imprinted genes. X chromosome inactivation is another mammalian-specific epigenetic mechanism, involving gene dosage compensation of genes on the sex chromosomes. It also plays an essential role in early mammalian development, although similar but different gene dosage mechanisms are known in other organisms. These examples clearly reveal that the mammalian genome inherits epigenetic information as ‘parental memories’ to the next generation as well as genetic information without DNA sequence alteration. These give a clear message: epigenetics is one of the fundamentals in modern biology.The birth of Dolly the sheep in 1996, the first cloned mammal from a somatic cell, is another epoch-making event in our understanding of mammalian biology, demonstrating that even terminally differentiated somatic cells can be reprogrammed in unfertilized eggs and regain totipotency of development to term. This, combined with the successful somatic cloning of several other mammalian species, provided conclusive evidence that development is operated by reversible epigenetic memories. The developmental process, in which fertilized eggs develop into multiple highly differentiated adult cells, was described by Waddington as ‘epigenetics’ to deal the phenotypic diversity of differentiated cells having identical genetic information. However, such epigenetic processes have long been considered as irreversible or one-way. Somatic cloning dramatically changed that. Epigenetics deals with heritable and reversible memories written in the genome that affect phenotypes without DNA sequence alteration.The production of induced pluripotent stem cells (iPS cells) in 2006 provided additional evidence that terminally differentiated somatic cells can be reprogrammed artificially, in this case by adding four transcription factors that play essential roles in maintaining stem cell features in embryonic stem cells (ES cells). Such transcription factors can break an epigenetic barrier formed by the action of DNA methylation, histone modification and chromatin-remodelling factors that determine each specific somatic cell type. In the famous ‘epigenetic landscape’ proposed by Waddington, it was suggested that genetic networks, as well as protein–protein interaction, underlie the formation of epigenetic landscape. DNA methylation, histone modification and chromatin remodelling factors are key players in epigenetic regulation. However, these factors may also be involved in ‘transient’ rather than ‘stable’ gene expression regulation; thus, the definition of epigenetics becomes a little bit vague and/or broader than the original one. Nevertheless, we can say that what is important for elucidating the developmental process is research on the interaction between genetic (transcription network) and epigenetic processes.Epigenetics is deeply involved in development and differentiation, and it is probable that it plays some essential roles in adaptive responses and evolutionary processes. We are now starting to understand how epigenetic state is altered in many of diseases and to recognize the slight differences that exist even between ES cells and iPS cells. That is why epigenetics is having considerable impact in the field of lifestyle-related diseases, reproductive and regenerative medicine. It is a big challenge to control cellular activities by regulating genetic and epigenetic factors and may be one of the most difficult barriers confronting present and future medicine. However, this is a necessary step towards safe and effective medicine.Several experts kindly contributed to this special issue entitled ‘mammalian epigenetics in biology and medicine’, by taking care of important topics on (i) epigenetic aspects in mammalian development [1–5], (ii) molecular mechanisms working in mammalian life cycle [6–9], and (iii) epigenetics in reprogramming technologies, human health and medicine [10–14].We are sure that readers of this issue will gain an understanding of how important epigenetics is as one of the central issues in the biology and medicine in the twenty-first century." @default.
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• W2139790010 title "Mammalian epigenetics in biology and medicine" @default.
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• W2139790010 doi "https://doi.org/10.1098/rstb.2012.0386" @default.
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