Beyond the Nucleosome: Epigenetic Aspects of Position–Effect Variegation in Drosophila

is a nearly ubiquitous feature of the eukaryotic chromosome. Although heterochromatin is not cytologically visIt is now widely recognized that heritable changes in gene ible in yeast, gene silencing phenomena with features expression can occur without accompanying changes similar to heterochromatin-induced gene inactivation in inDNA sequence. The discovery of position–effect varieDrosophila are observed in S. cerevisiae and S. pombe gation (PEV) by H. J. Muller in 1930 provided the first (reviewed by Grunstein, 1998 [this issue of Cell]). description of a phenomenon with an underlying epigeGeneral Models of PEV: cis-Spreading netic basis. Muller described mutations of the white and trans-Interactions (w) eye color gene of Drosophila that resulted in strikHow does heterochromatin induce variegated position ing, cell-to-cell variations in gene expression. The mosaic effects on euchromatic genes? Although several models phenotypes were caused by a chromosomal position have been proposed to explain the underlying basis effect in which a rearrangement breakpoint displaced of PEV in Drosophila, the most popular one envisions the w gene from its normal euchromatic location and the primary determinant to be the cis-spreading of a placed it in the vicinity of heterochromatin. Some recondensed, heterochromatic chromatin state past the arrangements resulted in large patches of red facets rearrangement breakpoint (Figures 1A and 1B). This cisadjacent to large white patches in the adult eye. This spreading model postulates that heterochromatin impattern of variegation suggested that a decision to exposes an altered chromatin conformation onto the eupress or repress the w gene was made early during chromatic gene, preventing access of the transcriptional tissue development and was maintained in a metastable machinery and resulting in transcriptional repression. state through multiple cell divisions. Variegation is accounted for by variations among cells PEV provides a model system to investigate the nature in the extent of linear spreading. Although the molecular of an imprint that specifies the transcriptional state of nature of the heterochromatin-induced change is una gene and the processes that influence its stability. Since heterochromatin can induce the inactivation of known, several lines of evidence suggest that PEV involves, or results in, changes in chromatin structure many, if not all, euchromatic genes in Drosophila, studies of PEV more generally address the functional differ(reviewed byElgin, 1997). Cytogenetic studieshave shown that the euchromatin adjacent to the rearrangement ences between heterochromatin and euchromatin. These