GENETIC-CHARACTERIZATION OF HDA1(+), A PUTATIVE FISSION YEAST HISTONEDEACETYLASE GENE

hda1(+) (histone deacetylase 1) is a fission yeast gene which is highl y similar in sequence to known histone deacetylase genes in humans and budding yeast. We have investigated if this putative histone deacetyl ase contributes to transcriptional silencing in the fission yeast Schi zosaccharomyces pombe. A precise deletion allele of the hda1(+) open r eading frame was created. Cells lacking the hda1(+) gene are viable. H owever, genetic analysis reveals that cells without hda1(+) display en hanced gene repression/silencing of marker genes, residing adjacent to telomeres, close to the silent mating-type loci and within centromere I. This phenotype is very similar to that recently reported for rpd3 mutants both in Drosophila and budding yeast. No defects in chromosome segregation or changes in telomere length were detected. Cells lackin g the hda1(+) gene display reduced sporulation. Growth of hda1 cells i s partially inhibited by low concentrations of Trichostatin A (TSA), a known inhibitor of histone deacetylase enzymes. TSA treatment is also able to overcome the enhanced silencing found in heterochromatic regi ons of hda1 cells. These results indicate a genetic redundancy with re spect to deacetylase genes and partially overlapping functions of thes e in fission yeast. The significance of these results is discussed in the light of recent discoveries from other eukaryotes.