A12 - Regulation of embryonic cell plasticity by stage-specific histone modification profiles
We have shown that stage-specific histone modification profiles coordinate cell differentiation during development. These profiles are sensitive to changes in mitotic activity, in particular with regard to repressive histone marks such as H4K20me3. Combining embryological, genetic, biochemical and computational analyses with genome-wide approaches, we will explore in the model organism Xenopus the molecular mechanisms, which turn altered HMPs into specific developmental phenotypes.
Figure 1: Heatmap detailing differential abundance of histone H3 and H4 modification states measured by tandem mass spectrometry (yellow-low, red-high abundance). The investigated developmental stages reflect key steps in embryonic development: Blastula – naïve multipotent; Gastrula – germ-layer specified; Neurula – germ layer patterning and differentiation; Tadpole – embryonic development completed.
Figure 2: Downregulating H4K20 trimethylation by microinjection of Suv4-20h Morpholino oligonucleotides in one half of the embryo blocks primary neurogensis (left) and eye formation (right). This phenotype arises from perturbation of the regulatory pathway shown at the bottom.