Fig. 7: A working model to explain the apparently different, but actually paralleled, phenotypes of the Set2/Setd2-null yeast, zebrafish and mouse.

The blue curves denote the levels of stresses that the organisms experience during normal development. The pink curve for yeast denotes an increased level of stress suffered by the yeast growing in nutrient depletion condition. The peaks of these curves are aligned vertically into two groups because they likely share conserved mechanisms in both nutrition and reproduction regulations. The red dashed lines denote the viability thresholds of different species when Set2/Setd2 is lost, and, therefore, the gray regions above the thresholds mean that only in this region where the Set2/Setd2-mediated epigenetic regulation is required. Therefore, if the peaks of the blue/pink curves reach above the red dashed lines, it means that the levels of stress are too high to be tolerated by the set2/setd2-null organism, thereby leading to lethality. In the cases of zebrafish, it is proposed that, as the stresses just reach (but not above) the viability threshold, they cause tolerable and apparently minor (but clearly significant) defects in the setd2-null zebrafish, thus explaining the non-requirement of setd2 in zebrafish development.