Fig. 3. Life and transcription in the absence of H3K4me1 at enhancers.

In wild-type Drosophila, Trr catalyzes H3K4me1 at enhancers, coincident with the presence of H3K27ac. In Trr protein null mutants, which are lethal, H3K4me1 is completely lost from enhancers and H3K27ac is strongly reduced. In addition, the coactivator protein UTX becomes destabilized in the absence of Trr. When Trr null mutants are complemented with either Trr lacking the SET methyltransferase domain (Trr∆SET) or Trr with a catalytically dead SET mutation (SET-CD), viability is rescued; however, H3K4me1 remains absent from enhancers. Expression of these mutant proteins also rescues stability of the UTX protein and partially restores H3K27ac at enhancers. Remarkably, when Trr null mutants are complemented with a small region of Trr that lacks all other known functional domains but is sufficient to stabilize UTX, this is sufficient to rescue viability.