Figure 9.

Model for the role of MLL PHD3 in activation and repression. Binding of PHD3 to H3K4me3 protects this mark from demethylation and possibly facilitates the propagation of the H3K4me3 mark, all leading to activation. When the CYP33 concentration is high, PHD3 preferentially binds to CYP33, resulting in the release of H3K4me3 from the MLL complex, loss of SET domain-mediated H3K4 methylation, increased nucleosome density, and concomitant repression. In addition, the CYP33 proline isomerase may act on the histone tail to enhance the addition of epigenetic marks for repression.