POSITION EFFECT VARIEGATION - AN EFFECT O F CHROMATIN ACTIVITY ON EUKARYOTIC GENES EXPRESSION

It is now well established that the eucaryotic nucleus is highly organ ized in euchromatic versus heterochromatic domains. Heterochromatin is mostly found in centromeric and telomeric regions of chromosomes wher eas chromosomal arms are essentially euchromatic. The proper expressio n of a gene strongly depends on its chromatin structure. For instance, when delocalized to a heterochromatic area, a euchromatic gene displa ys a mosaic inactivation. Silencing of gene expression by heterochroma tin is randomly distributed in some cells and is permanent. This pheno menon is named the position-effect variegation and has been extensivel y studied in Drosophila and yeast. Furthermore, similar silencing effe cts can also be observed in other organisms including mammals. In some cases, the epigenetic extinction of an allele can be transmitted to i ts homologous counterpart as shown by dominant variegation in Drosophi la 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 and abn ormal expansion of repeated sequences typically silencing gene express ion in Drosophila. Changes in chromatin conformation are widely observ ed in the epigenetic control of eucaryotic gene expression. The positi on-effect variegation provides a useful model to better understand chr omatin modification during development or during the cell cycle and ho w it is inherited by daughter cells leading to the permanent silencing of euchromatic genes.