[Epigenetics as an aspect of post-genomics].
A cell transmits to its progeny the activity level of many of its genes, not just their sequence. Just like the sequence may vary through a mutation, the gene activity level may change through an "epimutation" (an epigenetic modification) which is heritable and does not entail any concomitant genetic alteration. An epimutation can have important phenotypic consequences, that eventually survive to the loss of the environmental conditions that triggered it. For instance, epimutations are responsible for the divergence between a neuron and an epithelial cell that both come from the same egg and contain the same genome complement. This phenotypic difference is much larger than the one between the neurons from two animal species with dissimilar genotypes, thereby underlining the importance of epimutations. Tradition opposes the genetic and epigenetic visions, the latter being often adequated to the DNA methylation phenomenon. However, epimutations display a rich spectrum of modes that can all fit in a unique reference system based on correlated chemical, spatial and temporal scales. This reference system allows the integration of purely genetic mutations at one of its ends, thus paving the way to a new, gradual vision that encompasses the genome and the epigenome. At the other end can be found two types of epimutations that are both wide-ranging in space and rapid in producing phenotypic alterations. Firstly, long-range rearrangements of the three-dimensional structure of the chromosome may influence gene expression in an heritable fashion. Such rearrangements seem to result from the collective dynamics of DNA-related activities, particularly transcription. Lastly, heritable regulatory states, e.g. a differentiated state that results from tipping a regulatory "toggle switch", involve components that are distributed throughout the nucleus or the cytoplasm, and possibly all the way to cell confines.
Képès
François
F
Programme d'Epigénomique, Genopole, ATelier de Génomique Cognitive, CNRS UMR 8071/Genopole, 93, rue Henri-Rochefort, 91000 Evry, France. Francois.Kepes@genopole.cnrs.fr
D044127:Epigenesis, Genetic / Q000235:genetics*; D023281:Genomics