Tagging chromatin with retrotransposons: Target specificity of the Saccharomyces Ty5 retrotransposon changes with the chromosomal localization of Sir3p and Sir4p

Retrotransposon and retroviral insertions are not randomly distributed on chromosomes, suggesting that retroelements actively select integration sites. This is the case for the yeast Ty5 retrotransposons, which preferentially integrate into domains of silent chromatin at the HM loci and telomeres. Here we demonstrate that loss of Sir3p or Sir4p - components of silent chromatin - causes a greater than ninefold decrease in Ty5 targeting to the HM loci and largely randomizes chromosomal integration patterns. Strains with a deletion of SIR4 also display an ~10-fold increase in cDNA recombination, which is due both to the expression a- and α-mating-type information and the loss of Sir4p. It is known that in old yeast cells or in strains carrying the sir4-42 allele, the Sir complex relocalizes to the rDNA. About 26% of Ty5 insertions occur within the rDNA in sir4-42 strains compared with 3% in wild type. Ty5, therefore, is sensitive to changes in chromatin, indicating that retrotransposons may be useful for dissecting chromatin dynamics that occur during developmental programs such as aging.