Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein

The origin recognition complex (ORC) is an initiator protein for DNA replic ation, but also effects transcriptional silencing in Saccharomyces cerevisi ae and hetero chromatin function in Drosophila, It is not known, however, w hether any of these functions of ORC is conserved in mammals. We report the identification of a novel protein, HBO1 (histone acetyltransferase binding to ORC), that interacts with human ORC1 protein, the largest subunit of OR C. HBO1 exists as part of a multisubunit complex that possesses histone H3 and H4 acetyltransferase activities. A fraction of the relatively abundant HBO1 protein associates with ORC1 in human cell extracts. HBO1 is a member of the MYST domain family that includes S. cerevisiae Sas2p, a protein invo lved in control of transcriptional silencing that also has been genetically linked to ORC function. Thus the interaction between ORC and a MYST domain acetyltransferase is widely conserved, We suggest roles for ORC-mediated a cetylation of chromatin in control of both DNA replication and gene express ion.