A new member of the Sin3 family of corepressors is essential for cell viability and required for retroelement propagation in fission yeast

Tf1 is a long terminal repeat (LTR)-containing retrotransposon that propaga tes within the fission yeast Schizosaccharomyces pombe. LTR-retrotransposon s possess significant similarity to retroviruses and therefore serve as ret rovirus models. To determine what features of the host cell are important f or the proliferation of this class of retroelements, we screened for mutati ons in host genes that reduced the transposition activity of Tf1. We report here the isolation and characterization of pst1(+), a gene required for Tf 1 transposition. The predicted amino acid sequence of Pst1p possessed high sequence homology with the Sin3 family of proteins, known for their interac tion with histone deacetylases. However, unlike the SIN3 gene of Saccharomy ces cerevisiae, pst1(+) is essential for cell viability. Immunofluorescence microscopy indicated that Pst1p was localized in the nucleus. Consistent w ith the critical role previously reported for Sin3 proteins in the histone acetylation process, we found that the growth of the strain with the pst1-1 allele was supersensitive to the specific histone deacetylase inhibitor tr ichostatin A. However, our analysis of strains with the pst1-1 mutation was unable to detect any changes in the acetylation of specific lysines of his tones H3 and H4 as measured in bulk chromatin. Interestingly, the pst1-1 mu tant strain produced wild-type levels of TM-encoded proteins and cDNA, indi cating that the defect in transposition occurred after reverse transcriptio n. The results of immunofluorescence microscopy showed that the nuclear loc alization of the TM capsid protein was disrupted in the strain with the pst 1-1 mutation, indicating an important role of pst1(+) in modulating the nuc lear import of Tf1 virus-like particles.