Centromeres are heterochromatic in many organisms, but the mitotic function of this silent chromatin remains unknown. During cell division, newly replicated sister chromatids must cohere until anaphase when Scc1/Rad21-mediated cohesion is destroyed. In metazoans, chromosome arm cohesins dissociate during prophase, leaving centromeres as the only linkage before anaphase. It is not known what distinguishes centromere cohesion from arm cohesion. Fission yeast Swi6 (a Heterochromatin protein 1 counterpart) is a component of silent heterochromatin. Here we show that this heterochromatin is specifically required for cohesion between sister centromeres. Swi6 is required for association of Rad21-cohesin with centromeres but not along chromosome arms and, thus, acts to distinguish centromere from arm cohesion. Therefore, one function of centromeric heterochromatin is to attract cohesin, thereby ensuring sister centromere cohesion and proper chromosome segregation.

The ura4 + gene displays phenotypes consistent with variegated expression when inserted at 11 sites throughout fission yeast centromere 1. An abrupt transition occurs between the zone of centromeric repression and two adjacent expressed sites. Mutations in six genes alleviate repression of the silent-mating type loci and of ura4 + expressed from a site adjacent to the silent locus, mat3-M. Defects at all six loci affect repression of the ara4 + gene adjacent to telomeres and at the three centromeric sites tested. The clr4-$5 and rikl-304 mutations cause the most dramatic derepression at two out of three sites within cenl. All six mutations had only slight or intermediate effects on a third site in the center of cenl or on telomeric repression. Strains with lesions at the clr4, rikl, and swi6 loci have highly elevated rates of chromosome loss. We propose that the products of these genes are integral in the assembly of a heterochromatin-like structure, with distinct domains, enclosing the entire centromeric region that reduces or excludes access to transcription factors. The formation of this heterochromatic structure may be an absolute requirement for the formation of a fully functional centromere.[Key Words: S. pombe; PEV; heterochromatin; telomere; mating type] Received October 7, 1994; revised version accepted December 13, 1994.The centromeres of the fission yeast Schizosaccharomyces pombe are complex structures composed of large repetitive arrays symmetrically arranged around a nonrepetitive central domain (Hahnenberger et al. 1991;Murakami et al. 1991;Takahashi et al. 1992;Steiner et al. 1993; cenl is shown in Fig. 1A, below). Long arrays of tandem satellite repeats are frequently associated with the centromeres of many eukaryotes (Miklos and Cotsell 1990;Rattner 1991;Tyler-Smith and Willard 1993). These centromeric satellites are packaged into a highly compacted structure known as constitutive heterochromatin, but it is not known if this contributes to centromere function. It is likely that mammalian satellite repeats contribute to kinetochore formation, but alone, they may not be sufficient to form a functional centromere (Earnshaw et al. 1989;Haaf et al. 1992;Larin et al. 1994).Genes placed in the vicinity of centromeric heterochromatin in mouse cells can exhibit variable states of expression (Butner and Lo 1986). This phenomenon, termed position effect variegation (PEV), was first described in Drosophila, where it was found that genes placed adjacent to centromeric heterochromatin were unstably repressed (Eissenberg 1989;Henikoff 1990;Karpen 1994). In Drosophila, mouse, and human cells, some 1Corresponding author. studies indicate that heterochromatin is often associated with the nuclear periphery (Hochstrasser et al. 1986;Ferguson and Ward 1992;Vourc'h et al. 1993). It is possible that this and other associations serve to lock these regions of chromosomes in an inactive state (Karpen 1994}. In unicellular organisms, such as yeasts, there are chromosomal regions with features characteristic of heterochro...

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