DEVELOPMENTAL TIMING AND TISSUE-SPECIFICITY OF HETEROCHROMATIN-MEDIATED SILENCING

Heterochromatic position-effect variegation (PEV) describes the mosaic phenotype of a euchromatic gene placed next to heterochromatin. Heter ochromatin-mediated silencing has been studied extensively in Drosophi la, but the lack of a ubiquitous reporter gene detectable at any stage has prevented a direct developmental characterization of this phenome non, Current models attribute variegation to the establishment of a he ritable silent state in a subset of the cells and invoke differences i n the timing of silencing to explain differences in the patch size of various mosaic patterns, In order to follow the course of heterochroma tic silencing directly, we have generated Drosophila lines variegating for a lacZ reporter that can be induced in virtually all cells at any developmental stage. Our data indicate that silencing begins in embry ogenesis and persists in both somatic and germline lineages. A heterog eneity in the extent of silencing is also revealed; silencing is suppr essed in differentiated tissues but remains widespread in larval imagi nal discs containing precursor cells for adult structures, Using eye d evelopment as an example, we propose that the mosaic phenotype is dete rmined during differentiation by a variegated relaxation in heterochro matic silencing. Though unpredicted by prevailing models, this mechani sm is evident in other analogous systems.