Abstract
Histone acetylation and deacetylation are associated with transcriptional activity and the formation of constitutively silent heterochromatin. Increasingly, histone acetylation is also implicated in other chromosome transactions, including replication and segregation. We have cloned the only Schizosaccharomyces pombe MYST family histone acetyltransferase genes, mst1+ and mst2+. Mst1p, but not Mst2p, is essential for viability. Both proteins are localized to the nucleus and bound to chromatin throughout the cell cycle. Δmst2 genetically interacts with mutants that affect heterochromatin, cohesion, and telomere structure. Mst2p is a negative regulator of silencing at the telomere but does not affect silencing in the centromere or mating type region. We generated a census of proteins and histone modifications at wild-type telomeres. A histone acetylation gradient at the telomeres is lost in Δmst2 cells without affecting the distribution of Taz1p, Swi6p, Rad21p, or Sir2p. We propose that the increased telomeric silencing is caused by histone hypoacetylation and/or an increase in the ratio of methylated to acetylated histones. Although telomere length is normal, meiosis is aberrant in Δmst2 diploid homozygote mutants, suggesting that telomeric histone acetylation contributes to normal meiotic progression.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/.
ACKNOWLEDGMENTS
We thank Karl Ekwall, Robin Allshire, and Junko Kanoh for strains, Sally Pasion for discussion of unpublished results, and Lorraine Pillus, Angel Tabancay, and Will Dolan for helpful comments on the manuscript. We are grateful to Melissa Baker for assistance with the Q-PCR. We thank Ji-Ping Yuan for assistance with meiotic recombination assays. We thank Lorraine Pillus, Beverly Emerson, Dick McIntosh, and Paula Grissom for their hospitality and help to E.B.G. during the course of this work.
This study was supported by NIH grant R01 GM59321 to S.L.F.