The chromosomes of almost all higher eukaryotes contain regions, termed heterochromatin, that differ from the bulk of chromatin (euchromatin) in that they remain constitutively condensed throughout the cell-cycle. The DNA of heterochromatin consists almost entirely of repetitive sequences and encodes relatively few genes. Heterochromatin may play essential roles in mitosis, meiosis, gene expression and nuclear organization. The most well studied heterochromatin binding protein is the essential Drosophila heterochromatin binding protein 1 (HP1). HP1 is found in the heterochromatin of the chromocenter and in a limited number of other loci, including telomeres. HP1-like proteins have subsequently been identified in a number of species and share two regions with a high degree of amino acid conservation: an amino-terminal chromo domain (chromosome organization modifier), and a carboxy-terminal chromo shadow domain (Aasland and Stewart, 1995.) Both chromo and chromo shadow domains are able to target proteins to their site of action on chromatin. C. elegans mitotic chromosomes are holocentric and by definition do not have a localized centromeric region, nor do they have large tracts of heterochromatin. The C. elegans sequencing project, however, has identified two protein containing both chromo and chromo shadow domains, which we are now studying in our laboratory. hpl-1 maps on the right arm of the X chromosome, to the right of the unc-9 locus. Analysis of the genetic map of this region has not revealed the presence of any previously isolated candidate mutations for the hpl-1 locus. The other gene being studied hpl-2, maps to the middle of chromosome III. We are now testing whether the dominant maternal effect mutation mel-23, which maps to this region, corresponds to hpl-2 by microinjection rescue. We are also trying to isolate mutations in these two genes by a reverse genetic approach using Roberts Barstead method for isolating deletions in PCR screens of mutagenized populations. The study of HP1 homologues in C. elegans should shed light on the functions of this conserved family of proteins in an organism with vastly different chromosome organization and behaviour. Aasland and Stewart, N.A.R. 23:3168-3173

Affiliation:
- Institut de Zoologie, Universite de Fribourg, 1700 Fribourg, Switzerland