HP1 proteins—What is the essential interaction?

There are three mammalian HP1 genes, Cbx5 (encoding HP1alpha), Cbx1 (encoding HP1beta) and Cbx3 (encoding HP1gamma). Despite their high degree of sequence homology mutational analysis has revealed different phenotypes indicating that they possess different functions. Notably, the Cbx1 mutation is lethal in its homozygous condition. The Cbx1 null phenotype is therefore more severe than the Suv(3)9h1/h2 double-mutant mouse, indicating that the essential function of the Cbx1 gene product, HP1beta, is likely to lie outside its interaction with the heterochromatic H3K9me3 determinant of the "histone code" imposed by the Suv(3)9h1/h2 HMTases. Comparisons of HPI mutants in flies and fungi with corresponding mutations in Suv(3)9 genes show that HP1 mutations are invariably more severe than mutation in Suv(3)9 genes. The implications of these data for HP1 function are discussed.