Transcriptional Silencing in the Fission Yeast: A Manifestation of Higher Order Chromosome Structure and Functions

Abstract

Centromeres and telomeres perform a variety of important functions during the cell cycle. The cis-acting centromeric DNA nucleates the assembly of a large protein complex, the kinetochore, which performs several functions crucial for the faithful transmission of chromosomes to daughter nuclei. Sister chromatids remain tethered at the kinetochore until the transition from metaphase to anaphase. During prometaphase, sister kinetochores must capture microtubules emanating from opposite spindle poles, and only when all sister kinetochores on all chromosomes have achieved bilateral attachment can anaphase be triggered by dissolution of the link between sister kinetochores (Gorbsky 1995). Failure of centromere/kinetochore function leads to aberrant segregation of chromosomes due to nondisjunction or premature separation of sister chromatids, resulting in chromosome loss and gain. Since telomeres are required to protect the ends of linear chromosomes against replicative diminution, exonucleolytic degradation, and end-to-end fusion, loss of telomere function also results in the destabilization of chromosomes (Sandell and Zakian 1993).

In many organisms, both centromeres and telomeres are associated with large protein complexes that are frequently found to contact the nuclear periphery during interphase (Karpen 1994; Gilson et al. 1995). In addition, these chromosomal regions tend to be heterochromatic, transcriptionally silent, suppressed for recombination, and late-replicating (Karpen 1994; Palladino and Gasser 1994; Gilson et al. 1995). When reporter genes are placed within or adjacent to these regions, they regularly become subject to a form of epigenetic regulation. Although all cells in a population are genetically identical, some lineages express the gene, whereas in others it is repressed...