Histones are proteins that act to package DNA into chromatin. The methylation of lysine 4 on histone H3 is correlated with active gene expression in eukaryotes. In mammals, H3K4 is methylated by the MLL family of histone methyl transferases (HMTs). The catalytic subunits all share a SET domain, but full activity requires the presence of other complex components. One core component is Ash2L, which comprises a zinc-finger motif and a carboxy-terminal SP1a and ryanodine receptor (SPRY) domain. Chen et al. and Sarvan et al. have determined the structure of the N-terminal domain of human Ash2L. Both found that besides a zinc finger, the domain includes a winged-helix motif, a DNA binding motif that is often involved in transcription regulation. The zinc-finger domain was previously proposed to bind histone tails; however, in the context of the structure, it lacks features required for such binding. Sarvan et al. show that the Ash2L winged-helix domain is required for binding to the β-globin locus control region, H3K4 methylation, and maximal expression of the β-globin gene, whereas Chen et al. show that it binds preferentially to an active chromatin domain in a Homeobox gene locus and suggest that it may play a role in chromosome demarcation.
EMBO Rep. 12, 10.1038/embor.2011.101 (2011); Nat. Struct. Mol. Biol. 18, 10.1038/nsmb.2093 (2011).