HUMAN CENP-A CONTAINS A HISTONE H3 RELATED HISTONE FOLD DOMAIN THAT IS REQUIRED FOR TARGETING TO THE CENTROMERE

Centromeres are the differentiated chromosomal domains that specify th e mitotic behavior of chromosomes. To examine the molecular basis for the specification of centromeric chromatin, we have cloned a human cDN A that encodes the 17-kD histone-like centromere antigen, CENP-A. Two domains are evident in the 140 aa CENP-A polypeptide: a unique NH2-ter minal domain and a 93-amino acid COOH-terminal domain that shares 62% identity with nucleosomal core protein, histone H3. An epitope tagged derivative of CENP-A was faithfully targeted to centromeres when expre ssed in a variety of animal cells and this targeting activity was show n to reside in the histone-like COOH-terminal domain of CENP-A. These data clearly indicate that the assembly of centromeres is driven, at l east in part, by the incorporation of a novel core histone into centro meric chromatin.