COMPASS: A complex of proteins associated with a trithorax-related SET domain protein

The trithorax genes encode an evolutionarily conserved family of proteins t hat function to maintain specific patterns of gene expression throughout ce llular development. Members of this protein family contain a highly conserv ed 130- to 140-amino acid motif termed the SET domain. We report the purifi cation and molecular identification of the subunits of a protein complex in the yeast Saccharomyces cerevisiae that includes the trithorax-related pro tein Set1. This protein complex, which we have named COMPASS (Complex Prote ins Associated with Set1), consists of seven polypeptides ranging from 130 to 25 kDa. The same seven proteins were identified in COMPASS purified eith er by conventional biochemical chromatography or tandem-affinity tagging of the individual subunits of the complex. Null mutants missing any one of th e six nonessential subunits of COMPASS grow more slowly than wild-type cell s under normal conditions and demonstrate growth sensitivity to hydroxyurea . Furthermore, gene expression profiles of strains missing either of two no nessential subunits of COMPASS are altered in similar ways, suggesting thes e proteins have similar roles in gene expression in vivo. Molecular charact erization of trithorax complexes will facilitate defining the role of this class of proteins in the regulation of gene expression and how their misreg ulation results in the development of human cancer.