Solution structure, domain features, and structural implications of mutants of the chromo domain from the fission yeast histone methyltransferase Clr4

The encapsulation of otherwise transcribable loci within transcriptionally inactive heterochromatin is rapidly gaining recognition as an important mec hanism of epigenetic gene regulation. In the fission yeast Schizosaccharomy ces 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. Clr3 and its human and D rosophila homologs have been identified as histone MS-specific methyltransf erases, further implicating this family of proteins in chromatin remodeling . Our structure highlights a conserved surface that may be involved in chro me domain-ligand interactions. We have also analyzed two chrome domain muta nts (W31G and W41G) that previously were shown to affect silencing and swit ching in full-length Clr4. Both mutants are significantly destabilized rela tive to wild-type. (C) 2001 Academic Press.