Novel human HALR (MLL3) gene encodes a protein homologous to ALR and to ALL-1 involved in leukemia, and maps to chromosome 7q36 associated with leukemia and developmental defects

We have identified and characterized the similar to 12-kb cDNA of a novel h uman gene (designated HALR for "homologous to ALR" and given the symbol MLL 3 by the HUGO Gene Nomenclature Committee) for which open reading frame (OR F) encodes a predicted large hydrophilic nuclear protein comprising 4,025 a mino acids with a calculated molecular mass of similar to 443 kD. Within th e amino acid sequence of HALR were identified a SUVAR3-9, enhancer of zeste , trithorax (SET) domain, three plant homeodomain (PHD)-type zinc fingers, a high motility group (HMG)-1 box, a leucine-zipper-like pattern, two poten tial transactivating domains, several nuclear localization signals, and mul tiple nuclear receptor interaction signature motifs. Especially within the SET domain, PHD fingers and several other regions, the HALR protein exhibit s significant similarity to ALR (acute lymphoblastic leukemia [ALL]-1 relat ed), ALL-1/myeloid/lymphoid or mixed-lineage leukemia (ALL-1/MLL), and trit horax, evolutionarily conserved proteins that influence differentiation and development. Northern blot analysis demonstrated transcripts of similar to 11-12 kb, while reverse transcriptase-polymerase chain reaction (RT PCR) r evealed that HALR is expressed in a wide range of human tissues and cancer cell lines. The HALR gene contains 46 exons, is estimated to span >101 kb, and is located on chromosome region 7q36. Terminal 7q deletions are common chromosomal aberrations encountered in hematological neoplasia and in holop rosencephaly 3, a midline embryonic defect involving forebrain development. We have also isolated the partial cDNA of the murine homologue of HALR, wh ich displays high homology to its human counterpart, Taking into considerat ion its notable protein motifs, ubiquitous expression, evolutionary conserv ation and chromosomal position, HALR is likely to play a housekeeping role in transcriptional regulation, and may be involved in leukemogenesis and de velopmental disorders.