The encapsulation of otherwise transcribable loci within transcriptionally 
inactive heterochromatin is rapidly gaining recognition as an important 
mechanism of epigenetic gene regulation. In the fission yeast 
Schizosaccharomyces pombe, heterochromatinization of the mat2/mat3 loci silences 
the mating-type information encoded within these loci. Here, we present the 
solution structure of the chromo domain from the cryptic loci regulator protein 
Clr4. Clr4 is known to regulate silencing and switching at the mating-type loci 
and to affect chromatin structure at centromeres. Clr4 and its human and 
Drosophila homologs have been identified as histone H3-specific 
methyltransferases, further implicating this family of proteins in chromatin 
remodeling. Our structure highlights a conserved surface that may be involved in 
chromo domain-ligand interactions. We have also analyzed two chromo domain 
mutants (W31G and W41G) that previously were shown to affect silencing and 
switching in full-length Clr4. Both mutants are significantly destabilized 
relative to wild-type.