Epigenetics – November 2013
The term “epigenetics” was coined by Conrad Waddington in the 1940s, to describe the causal mechanisms of development from the fertilized egg to adult. Epigenetics is now used to refer to heritable chromatin modifications that control gene expression without changes in DNA sequence. The study of epigenetics, building on genomics and molecular biology, holds great promise in understanding the normal and diseased state of life.
Distinct epigenetic processes include chemical modifications of DNA or DNA-associated proteins, such as histones. Methylation of DNA, histone modifications and higher-order chromatin structure are central to the regulation of mammalian genome organization. The combination of epigenetic modifications in a genome comprises the epigenome, which adds an extra layer of supervision and complexity to the genome of a cell by altering, revising and rewriting the genomic language written in the DNA sequence. Epigenetic modifications (epigenetic marks) are critical for cell development and specialization during embryogenesis as well as for normal processes such as X-chromosome inactivation in female mammals. They are transmitted transgenerationally, but the epigenetic state of cells can also be altered by environmental stresses and by physiological aging.
The relevance of epigenetic alterations in the initiation and progression of cancer and other pathologies is increasingly being acknowledged. In response to changes in the external environment, chromatin and chromosomes experience profound and dynamic organizational modifications. During the division of a cell, chromosomes condense and relax. Damaged DNA acquires a particular conformation that assists its repair. Central for the functionality of the cell, a significant part of the genome must be maintained in a repressed state, which differs between distinct cell types. Conversely, other genes need to be maintained in a transcriptionally active state. These repressive/activating epigenetic processes are finely controlled to preserve the genome’s integrity and the relevant cell function. The epigenetic signature of any cell reveals key insights into its cellular state and fitness. Increasing our understanding of the epigenome will greatly enlarge our knowledge of health and disease.
Currently, the field of epigenetics is transiting through a documentation phase, a common characteristic of a branch of science that is evolving rapidly. Despite great advancement in recent years, we still do not really understand how the genome and epigenome interact and how this interaction confers plasticity and adaptability to a cell. It is still not clear whether specific epigenetic modifications can be classified as adaptive or adverse. Given the effort devoted to epigenetics research, these areas of ignorance will hopefully be clarified in the near future.
This Virtual Issue comprises a collection of research papers and reviews recently published in the FEBS Journal on the influence of chromatin and chromosome organization on gene expression and the roles of epigenetic mechanisms in development and disease.
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