Position-effect control at the silent
mat2-mat3 interval and at centromeres and telomeres in fission yeast is
suggested to be mediated through assembly of heterochromatin-like
structures. Therefore, trans-acting genes that affect silencing may
encode either chromatin proteins, factors that modify them or factors
that affect chromatin assembly. Here, we report the identification of an
essential gene, clr6 (cryptic loci regulator), encoding a putative
histone deacetylase, which when mutated affects epigenetically-maintained repression at the mat2-mat3 region and at centromeres and
reduces the fidelity of chromosome segregation. Furthermore, we show
that the Clr3 protein, which regulates silencing at the mat2-mat3 region
and at centromeres and telomeres, also shares strong homology to known
histone deacetylases. Genetic analyses indicate that histone
deacetylation in fission yeast might be regulated by at least two
overlapping mechanisms. We also found that transient inhibition of
histone deacetylase activity by trichostatin A results in the increased
missegregation of chromosomes in subsequent generations and, remarkably,
alters the imprint at the mat locus, causing the heritable conversion of
the repressed epigenetic state to the expressed state. This work
supports the model that the level of histone deacetylation has a role in
the assembly of repressive heterochromatin and provide insight into the
mechanism of epigenetic inheritance. Research sponsored by National
Cancer Institute, DHHS, under contract with ABL
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