Heritable inactivation of specific regions of the genome is a widespread, 
possibly universal phenomenon for gene regulation in eukaryotes. 
Self-perpetuating, clonally inherited chromatin structure has been proposed as 
the explanation for such phenomena as position-effect variegation (PEV) and 
control of segment determination and differentiation in flies, X-chromosome 
inactivation and parental imprinting in mammals, gene silencing by paramutation 
in maize and silencing of the mating-type loci in yeasts. We have now found that 
the clr4 gene, which is essential for silencing of centromeres and the 
mating-type loci in Schizosaccharomyces pombe, encodes a protein with high 
homology to the product of Su(var)3-9, a gene affecting PEV in Drosophila. Like 
Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins 
that modulate chromatin structure. Site-directed mutations in the conserved 
residues of the chromo domain confirm that it is required for proper silencing 
and directional switching of the mating type, like SET domain. Surprisingly, RNA 
differential display experiments demonstrated that clr4+ can mediate 
transcriptional activation of certain other loci. These results show that clr4 
plays a critical role in silencing at mating-type loci and centromeres through 
the organization of repressive chromatin structure and demonstrate a new, 
activator function for Clr4p.