10 Telomere Position Effect: Silencing Near the End

Abstract

HETEROCHROMATIC SILENCING IS DISTINCT FROM TRANSCRIPTIONAL GENE REPRESSION
The organization of genomes into heterochromatic and euchromatic regions is a global method of gene regulation, in contrast to single-gene transcriptional control. Originally defined cytologically in higher organisms as dark-staining chromatin, heterochromatin is now characterized by a collection of molecular markers including repetitive DNA, regular nucleosome spacing, low gene density, late S phase replication, and histone tail modifications including hypoacetylation (for review, see Henikoff 2000; Richards and Elgin 2002). Heterochromatin is often found at centromeric and telomeric loci, and active genes that are translocated to heterochromatin are heritably silenced, often in a mosaic or variegated pattern from cell to cell. This variegation is thought to reflect a stochastic heterochromatin assembly at a formerly euchromatic locus. Termed “facultative heterochromatin,” these genes are silent in only a subset of the cells, as opposed to “constitutive heterochromatin,” where silencing is stable in all cells (for review, see Richards and Elgin 2002).

Heterochromatic transcriptional silencing is distinct from transcriptional repression seen at individual promoters that occurs at particular times in the cell cycle or during organismal development. Unlike the mechanisms of repression at specific promoters, heterochromatic silencing is generally promoter-nonspecific, such that almost all promoters are silenced by heterochromatin. Heterochromatin constitutes a repressive environment for gene expression over a large distance, in contrast to gene-specific transcriptional repression that occurs over the relatively short range of the individual gene. Certain histone modifications associated with reduced transcription are found in both heterochromatic silencing and gene-specific transcriptional repression (see,...