The evolution of epigenetic developmental gene regulation

The evolution of animal form is believed to have occurred largely through changes in gene regulatory networks controlling developmental processes. These complex networks consist of transcription factors, which are largely conserved across animal phyla, and their target genes. There is growing evidence that epigenetic mechanisms support the function of these transcriptional networks by regulating the accessibility of chromatin throughout development. Basal animal phyla are important models to gain insights into the evolution of transcriptional networks and their interplay with epigenetic modifications, yet no information on epigenetic regulation exists in animals outside the Bilateria. I will study the regulation of gene expression in Nematostella vectensis, which represents a sister group to the Bilateria. I plan to determine the genome-wide distribution of a Polycomb mediated histone modification to investigate if Polycomb mediated repression of developmental regulators is as complex in Nematostella as it is in bilaterian model organisms. I will also use characteristic chromatin signatures previously identified in mammalian cells to map transcriptional regulatory elements throughout the genome. Their functionality will be tested in transgenic Nematostella polyps, and their complexity compared to that in Bilaterians. These studies should provide crucial insights into the evolution of cis-regulatory elements and epigenetic silencing in transcriptional networks and how this contributed to the increasing complexity of animal body plans.

The complex regulation of gene expression as it can be found in all animals, including humans, evolved at least 600 Million years ago. This is a theory suggested by our findings that the so called gene regulatory landscape in the sea anemone Nematostella vectensis is highly similar to the regulatory landscapes of higher organisms like fruit flies and zebrafish. Sea anemones can look like colorful underwater plants, however, they are actually predatory animals related to jelly fish and corals. Together, these animals form a group called Cnidaria, which is thought to have split from most remaining animals, grouped into the Bilateria, about 600 Million years ago. Cnidarians are characterized by a much simpler body plan compared to bilaterians, for example, they have only two (instead of three) germ layers. How our body works and looks is largely the result of the action of our genes and how they interact, regulating each others activity in so called gene regulatory networks. Sequencing of the human and animal genomes has shown that anatomically simple and evolutionary basal organisms like sea anemones show a surprisingly complex gene make-up that is similar to that of more complex organisms like humans or fruit flies. This suggests that the evolution of more complex organisms cannot be explained simply by the presence or absence of individual genes. In the course of my Hertha Firnberg project, I analyzed if the differences in complexity between sea anemones and species representing the more complex bilaterians (fruit flies and zebrafish), could be explained by differences in the distribution of gene regulatory sequences. To this end I adapted a sophisticated molecular approach called chromatin immunoprecipitation for use in sea anemones. This led to the identification of gene regulatory elements throughout the entire genome of the sea anemone. I then compared the resulting data to the gene regulatory landscapes of more complex organisms. Since the sea anemone shows a complex landscape of gene regulatory elements similar to the fruit fly or other model animals, I believe that the principle of complex gene regulation was already present in the common ancestor of human, fly and sea anemone some 600 million years ago.