The conserved DPY-30 is an essential component of the dosage compensation 
complex that balances the X-linked gene expression by regulation of the complex 
formation in Caenorhabditis elegans. The human DPY-30-like protein (DPY-30L) 
homolog is a conserved member of certain histone methyltransferase (HMT) 
complexes. In the human MLL1 (mixed-lineage leukemia-1) HMT complex, DPY-30L 
binds to the BRE2 homolog ASH2L in order to regulate histone 3-lysine 4 
trimethylation. We have determined the 1.2-A crystal structure of the human 
DPY-30L C-terminal domain (DPY-30L(C)). The DPY-30L(C) structure, harboring the 
conserved DPY-30 motif, is composed of two alpha-helices linked by a sharp loop 
and forms a typical X-type four-helix bundle required for dimer formation. 
DPY-30L(C) dimer formation is largely mediated by an extensive hydrophobic 
interface with some additional polar interactions. The oligomerization of 
DPY-30L(C) in solution, together with its reported binding to ASH2L, leads us to 
propose that the hydrophobic surface of the dimer may provide a platform for 
interaction with ASH2L in the MLL1 HMT complex.