pitkin(D), a novel gain-of-function enhancer of position-effect variegation, affects chromatin regulation during oogenesis and early embryogenesis indrosophila

The vast majority of the >100 modifier genes of position-effect variegation (PEV) in Drosophila have been identified genetically as haplo-insufficient loci. Here, we describe pitkin(Dominant) (ptn(D)), a gain-of-function enha ncer mutation of PEV. Its exceptionally strong enhancer effect is evident a s elevated spreading of heterochromatin-induced gene silencing along euchro matic regions in variegating rearrangements. The ptn(D) mutation causes ect opic binding of the SU(VAR)3-9 heterochromatin protein at many euchromatic sites and, unlike other modifiers of PEV, it also affects stable position e ffects. Specifically, it induces silencing of white(+) transgenes inserted at a nide variety of euchromatic sites. ptn(D) is associated with dominant female sterility. +/+ embryos produced by Ptn(D)/+ females mated with wild- type males die at the end of embryogenesis, whereas the ptn(D)/+ sibling em bryos arrest development at cleavage cycle 1-3, due to a combined effect of maternally provided mutant product and an early zygotic lethal effect of p tn(D). This is the earliest zygotic effect of a mutation so far reported in Drosophila. Germ-line mosaics show that;ptn(+) function is required for no rmal development in the female germ line. These results, together with effe cts on PEV and white(+) transgenes, are consistent with the hypothesis that the ptn gene plays an important role in chromatin regulation during develo pment of the female germ line and in early embryogenesis.