L'effet de position : influence de la conformation chromatinienne sur l'expresson des gènes eucaryotes

Abstract

It is now well established that the eucaryotic nucleus is highly organized in euchromatic versus heterochromatic domains. Heterochromatin is mostly found in centrometric and telomeric regions of chromosomal arms are essentially euchromatic. The proper expression of a gene strongly depends on its chromatin structure. For instance, when delocalized to a heterochromatic area, a euchromatic gene displays a mosaic inactivation. Silencing of gene expression by heterochromatin is randomly distributed in some cells and is permanent. This phenomenon is named the position-effect variegation and has been extensively studied in Drosophila and yeast. Furthermore, similar silencing effects canalso be observed in other organisms including mammals. In some cases, the epigenetic extinction of an allele can be transmitted to its homologous conterpart as shown by dominant variegation in Drosophila or paramutation in plants. Similar effects involving cis and trans-inactivating chromatin structure might also be responsible for certain human dominant diseases of the nervous system associated with an abnormal expansion of repeated sequences typically silencing gene expression in Drosophila. Changes in chromatin conformation are widely observed in the epigenetic control of eucaryotic gene expression. The position-effect variegation provides a useful model to better understand chromatin modification during development or during the cell cycle and how it is inherited by daughter cells leading to the permanent silencing of euchromatic genes.