Epigenetics: development, dynamics and disease.

Abstract

With the discovery of epigenetic mechanisms that regulate the development and function of cells and tissues, the life sciences have entered a novel area of disease-relevant research. Epigenetic modifications can be highly dynamic alterations in DNA and chromatin and, thereby, they differ from changes at the level of the DNA sequence itself, i.e. by mutations, or at the level of DNA structure, e.g. translocations. Epigenetic mechanisms are central to the regulation of cell-type-specific physiology and pathology. Cell–specific gene expression and hence cellular phenotypes are epigenetically controlled by marking histones through chemical modifications and DNA through methylation, but also through other mechanisms such as incorporation of histone variants, transcription of non– coding RNAs, RNA editing and chromatin remodelling. These epigenetic mechanisms are discussed in this special issue from various angles including basic, translational and applied clinical research. The fundamental understanding of epigenetic mechanisms opens a new window for changing the transcriptional states of cells, tissues and organs, both in physiological and disease states. With the selection of the articles and viewpoints within this special issue, our aim here is to foster cross talk between basic and applied epigenetic science. Such strong interdisciplinary research should lead to potential future benefits for improved medical care of patients that suffer from diseases in which epigenetic functions are derailed, or even for preventive measures for avoiding the development of epigenetically driven diseases. The following provides an overview of the topics discussed in this special issue of Cell and Tissue Research on “Epigenetics”. The series of articles starts with recent advances in basic research to improve our understanding of the roles of histone variants, the dynamics during cell division, signal transduction to chromatin, the view of specific regulatory elements in the genome, interaction between chromatin modifiers and non–coding RNAs, and the role of RNA editing. The article by Biterge and Schneider (2014) gives a comprehensive overview of histone variants and their peculiarity with regard to temporal expression patterns and mRNA characteristics. Incorporation of variants within the chromatin broadens the plethora of mechanisms for regulating gene expression, as these variants not only influence nucleosome stability and shape distinct chromatin domains, but are also implicated in DNA repair. Although many aspects are not fully understood as yet, e.g. the function of histone variants and their recruitment and incorporation into chromatin, growing evidence indicates that the variants are of clinical importance. The role of histone modifications in chromatin dynamics in the cell cycle is presented by Doenecke (2014). Within this classical field of epigenetics, the author provides a comprehensive overview of the implications of histones in the transition from an open chromatin conformation in the interphase to a tightly packed chromatin that is the hallmark of mitotic chromosomes. Within this transition, histone modifications and histone variants play pivotal roles in the various accompanying processes. These include the establishment of Tanja Vogel and Silke Lassmann are members of the DFG Collaborative Research Center 992 “Medical Epigenetics”. Silke Lassmann is an associated member of BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany, and is also a member of the German Consortium for Translational Cancer Research (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.