Effects of repetitiveness, pairing and linkage on position-effect variegation in Drosophila

Abstract

Position-effect variegation (PEV) is a long distance silencing effect that results in variable inactivation of one or many genes. PEV is caused by the abnormal juxtaposition of heterochromatin and euchromatin following chromosome breakage. By using artificially constructed transgene arrays, I have found that the effects of PEV can be modified by changes in the local repetitiveness of a genetic region. Interestingly, this modification takes place at a distance from the breakpoint, suggesting that the control of variegation does not occur only at the point of propagation. I here propose a new model, emphasizing the role of paired repetitive elements, to account for heterochromatization and for the propagation of PEV. In addition, by using the phenomenon of dominant PEV, I compare the relative contribution of intrachromosomal and allelic pairing to trans-silencing in Drosophila, look at the effects of chromosomal location on dominant PEV, and examine a large array that does not seem to be prone to variegation, in spite of its repetitive nature. Finally, I review the history of chromosomal pairing phenomena and suggest a mechanism that might unify many known pairing and homology-sensing effects in diverse organisms.