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• Supplemental Table S1
  

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• Supporting Figure S1
  

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• Methods
  

The Mixed-Lineage Leukemia-1 (MLL1) 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 have determined the human genomic binding sites of MLL1. We find that MLL1 functions as the human equivalent of yeast Set1. Like Set1, MLL1 localizes with Pol II to the 5' end of actively transcribed genes, where histone H3 lysine 4 (H3-K4) trimethylation occurs. Consistent with this global role in transcription, MLL1 also localizes to micro-RNA (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 the dual roles MLL1 plays in maintenance of cellular identity.