Dynamics and stability: epigenetic conversions in position effect variegation

Abstract

Position effect variegation (PEV) refers to quasi-stable patterns of gene expression that are observed at specific loci throughout the genomes of eukaryotes. The genes subjected to PEV can be completely silenced or fully active. Stochastic conversions between these 2 states are responsible for the variegated phenotypes. Positional variegation is used by human pathogens (Trypanosoma, Plasmodium, and Candida) to evade the immune system or adapt to the host environment. In the yeasts Saccharomyces cerevisiae and S accharomyces pombe, telomeric PEV aids the adaptation to a changing environment. In metazoans, similar epigenetic conversions are likely to accompany cell differentiation and the setting of tissue-specific gene expression programs. Surprisingly, we know very little about the mechanisms of epigenetic conversions. In this article, earlier models on the nature of PEV are revisited and recent advances on the dynamic nature of chromatin are reviewed. The normal dynamic histone turnover during transcription and DNA replication and its perturbation at transcription and replication pause sites are discussed. It is proposed that such perturbations play key roles in epigenetic conversions and in PEV.