EpigeneticsConcepts, Theories, Paradigms and Mechanisms

Epigenetics concerns all meiotically and mitotically heritable changes in gene function that cannot be explained by changes in DNA sequence. It underlies the cellular diversity in multicellular organisms: although all cells have the same genetic constitution, the manner in which this genetic information is read out is different and many... read moreof these epigenetic differences in gene expression are set up during development and are then stably maintained throughout the cell cycle including mitosis.

Epigenetics also underlies phenotypic variability not predicted by Mendelian genetics. Epimutations can affect phenotype in a seemingly stochastic manner and are unstable and easily reversible compared to mutations of DNA sequence.

The impact of epigenetics on diseases such as cancer has only recently begun to be fully appreciated. To name but a few examples, disrupted DNA methylation patterns are a hallmark of tumorigenesis and the mistargeting of chromatin modifying enzymes and DNA repair proteins can clearly lead to abnormal changes in gene expression as well as compromising the integrity of the genome.

Major breakthroughs in our understanding of the molecular mechanisms underlying epigenetics have been made over recent years. So far, the major epigenetic modifiers are DNA methylation, RNA-associated silencing and histone modifications. Although these systems appear to be closely inter-related, the nature of these interactions and the relative importance of different epigenetic marks can vary considerably between species and even between cell types within the same species. This variability can clearly have an impact on the frequency of “epimutations”.

This series aims to bring together some of the major players in the field of epigenetics. A philosophical and historical perspective will be provided by the first two talks. Many of the other talks should illustrate cross-talk between different epigenetic processes (histone modifications, DNA methylation, non-coding RNAs and small interfering RNAs) in a variety of systems (from yeast to man). The role of nuclear organization in the establishment and maintenance of differential states of gene expression will be covered.