James F . Crow and William F . Dove A Reconsideration of the Mechanism of Position Effect Steven Henikoff

T HE title of this article was chosen for two reasons. First, it is the title of a remarkable article published 50 years ago by BORIS EPHRUSSI and EILEEN SUTTON aimed at explaining a widely studied but enigmatic phenomenon (EPHRUSSI and SUTTON 1944). But in addition, by highlighting ideas presented in that article, I will be reconsidering the mechanism of position effect in light of recent work suggesting that EPHRUSSI and SUTTON’S explanations were largely correct. Reconsideration includes resuscitation: while their article received attention in an early review on position effect (LEWIS 1950), it is barely mentioned in most reviews written since (BAKER 1968; SPOFFORD 1976; EISSENBERG 1989; TARTOF et al. 1989; SPRADLING and KARPEN 1990; GIUGLIATTI 1991; REUTER and SPIERER 1992). Position effects on gene expression fall into two classes. Somatically stable position effects were originally seen as rare spontaneous occurrences, such as the Bar locus duplication ( STURTEVANT 1925). With the advent of germline transformation, stable position effects on transgenes were found to be very common (WILSON et al. 1990). These xamples of position effect have proven to be extremely valuable, both for generating “enhancer trap” lines where these position effects are used to detect genes of developmental interest (O’KANE and GEHRING 1987) and for identifylng boundary elements that insulate against position effects (KELLUM and SCHEDL 1991). Stable position effects on transgenes can be understood in terms of the interaction between tissue-specific regulatory elements and promoters of position-affected genes. In contrast to stable position effects, somatically unstable, or variegated, position effects associated with chromosomal rearrangements (MULLER 1930) have resisted explanation. Positioneffect variegation (PEV) is observed as a random mixture of mutant and wild-type tissue that occurs for genes close to a newly created euchromatin-heterochromatin junction. In squashes of salivary gland polytene chromosomes, a position-