The mixed-lineage leukemia (MLL1/ALL-1/HRX) histone methyltransferase is 
involved in the epigenetic maintenance of transcriptional memory and the 
pathogenesis of human leukemias. To understand its role in cell type 
specification, we determined the human genomic binding sites of MLL1. We found 
that MLL1 functions as a human equivalent of yeast Set1. Like Set1, MLL1 
localizes with RNA polymerase II (Pol II) to the 5' end of actively transcribed 
genes, where histone H3 lysine 4 trimethylation occurs. Consistent with this 
global role in transcription, MLL1 also localizes to microRNA (miRNA) loci that 
are involved in leukemia and hematopoiesis. In contrast to the 5' proximal 
binding behavior at most protein-coding genes, MLL1 occupies an extensive domain 
within a transcriptionally active region of the HoxA cluster. The ability of 
MLL1 to serve as a start site-specific global transcriptional regulator and to 
participate in larger chromatin domains at the Hox genes reveals dual roles for 
MLL1 in maintenance of cellular identity.