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Vol. 10, Issue 10, 3171-3186, October 1999
¶
*Department of Molecular, Cellular and Developmental Biology,
University of Colorado, Boulder, Colorado 80309-0347;
Although silencing is a significant form of transcriptional
regulation, the functional and mechanistic limits of its conservation have not yet been established. We have identified the
Schizosaccharomyces pombe hst4+ gene as a
member of the SIR2/HST silencing gene
family that is defined in organisms ranging from bacteria to humans.
hst4Washington University School of Medicine, St. Louis,
Missouri 63110; §Department of Molecular Biology and
Genetics, Johns Hopkins University School of Medicine, Baltimore,
Maryland 21205; and Medical Research Council
Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU,
United Kingdom
mutants grow more slowly than wild-type cells
and have abnormal morphology and fragmented DNA. Mutant strains show
decreased silencing of reporter genes at both telomeres and
centromeres. hst4+ appears to be important
for centromere function as well because mutants have elevated
chromosome-loss rates and are sensitive to a microtubule-destabilizing
drug. Consistent with a role in chromatin structure, Hst4p localizes to
the nucleus and appears concentrated in the nucleolus.
hst4 mutant phenotypes, including growth and
silencing phenotypes, are similar to those of the Saccharomyces cerevisiae HSTs, and at a molecular level,
hst4+ is most similar to
HST4. Furthermore, hst4+ is a
functional homologue of S. cerevisiae HST3 and
HST4 in that overexpression of
hst4+ rescues the temperature-sensitivity
and telomeric silencing defects of an hst3 hst4
double mutant. These results together demonstrate that a
SIR-like silencing mechanism is conserved in the
distantly related yeasts and is likely to be found in other organisms
from prokaryotes to mammals.
Present address: Department of Biology,
Pacific Hall 0347, 9500 Gilman Drive, University of California, San
Diego, La Jolla, CA 92093-0347.
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