Fig. 7: A model for the functional regulation of DNMT3A.
From: Structural insight into hierarchical DNMT3A autoinhibition and its dysregulation in disease
Under the hierarchical autoinhibitory regulation, DNMT3A shows the highest activity on H3K4me0/K36me2-modified nucleosomes but the lowest activity on H3K4me3-modified nucleosomes. The disease-associated PWWP-ADD interface mutations lead to impaired DNMT3A autoinhibition and target selectivity, such as decreased activity on the H3K4me0/K36me2 region but increased activity on the H3K4me3 region, which may contribute to disease progression.
