NUCLEAR PUNCTATE DISTRIBUTION OF ALL-1 IS CONFERRED BY DISTINCT ELEMENTS AT THE N-TERMINUS OF THE PROTEIN

The ALL-I gene positioned at 11q23 is directly involved in human acute leukemia either through a variety of chromosome translocations or by partial tandem duplications. ALL-I is the human homologue of Drosophil a trithorax which plays a critical role in maintaining proper spatial and temporal expression of the Antennapedia-bithorax homeotic genes de termining the fruit fly's body pattern. Utilizing specific antibodies, we found that the ALL-I protein distributes in cultured cells in a nu clear punctate pattern. Several chimeric ALL-I proteins encoded by pro ducts of the chromosome translocations and expressed in transfected ce lls showed similar speckles. Dissection of the ALL-I protein identifie d within its approximate to 1,100 N-terminal residues three polypeptid es directing nuclear localization and at least two main domains confer ring distribution in dots. The latter spanned two short sequences cons erved with TRITHORAX. Enforced nuclear expression of other domains of ALL-I, such as the PHD (zinc) fingers and the SET motif, resulted in u niform nonpunctate patterns. This indicates that positioning of the AL L-I protein in subnuclear structures is mediated via interactions of A LL-I N-terminal elements. We suggest that the speckles represent prote in complexes which contain multiple copies of the ALL-I protein and ar e positioned at ALL-I target sites on the chromatin. Therefore, the ro le of the N-terminal portion of ALL-I is to direct the protein to its target genes.