We use comparative epigenomics to understand how gene regulatory mechanisms evolve. This, in turn, can inform us about how major evolutionary transitions occurred. To achieve this, we focus on non-conventional species, from unicellular eukaryotes (protists) to non-bilaterian animals such as sponges, ctenophores, or cnidarians. However, we are always excited to take a look at diverse branches of the Tree of Life. And sometimes, we reluctantly use classic model organisms.
METHYLEVOL - ERC-StG
Cytosine DNA methylation in eukaryotes
5mC is the most widespread base modification in eukaryotes. However, the way it is deposited across the genome and its associated functions vary greatly across lineages (see our recent review). For instance, Transposable Elements (TE) are known to be targeted by 5mC in plants, fungi, algae and animals. Similarly, Gene Body Methylation is present in plants, green algae and animals. However, how these patterns emerged in evolution is still unclear, since we lack information from many important clades. The difficulty to obtain a more diverse perspective on 5mC patterns resides on the pervasive tendency for secondary loss of DNA methylation in most lineages. Model systems such as Drosophila melanogaster, Caenorhabditis elegans or yeast are amongst them. We want to fill in these gaps by focusing on so far neglected eukaryotic diversity, establishing molecular tools to understand the roles of 5mC across divergent taxa. The ultimate goal is to uncover the ancestral states predating major eukaryotic groups, finding how this epigenetic mark originated in the Last Eukaryotic Common Ancestor and how it acquired its extant roles in genome regulation.
Invertebrate DNA methylation: variation and function
The animal kingdom is a puzzling group regarding 5mC patterns, since a lot of variation occurs across phyla. Most of our knowledge about DNA methylation comes from vertebrate systems. However, vertebrates are exceptional since they have hypermethylated genomes, in which almost all CpGs are fully methylated (with exceptions, see our work about sponges). Most invertebrate lineages sampled to date present much more sparse methylation, mostly enriched on broadly transcribed gene bodies (GbM), yet some have TE methylation (see for instance our work on centipedes). Particularly, the early lineages of the animal kingdom display strikingly different methylation patterns. We want to advance our knowledge on the variation of methylation patterns, the possible causes behind this variation and test the function of 5mC and its associated enzymes in understudied animal lineages.
Evolution of 5mC readers
Ultimately, the link between eukaryotic DNA methylation patterns and their regulatory roles are the proteins able to read and interpret 5mC. However, most of these proteins remain uncharacterised across most eukaryotic diversity. We want to test the evolutionary conservation of these proteins using a combination of molecular and bioinformatic approaches. We have previously found that NRF is an animal-specific Transcription Factor which is repelled by 5mC from sponges to humans, indicating that methyl-sensitivty might have shaped regulatory networks throughout animal evolution.
Host-gene capture by
Transposable Elements (TEs) are capable of jumping and expanding within host genomes in almost all eukaryotic lineages. Furthermore, TEs seem to have been already present back from the LECA, co-existing with host genomes for billions of years. Eukaryotic cells, in turn, defend themselves from these genomic parasites using chromatin components aimed at silencing TEs. Yet, we have found that TEs are able to acquire genes derived from host genes, in a process mirroring TE-domestication by host genomes. Interestingly, these captured genes are involved in chromatin regulation, including DNA methyl-transferases (see our work on dinoflagellates and charophytes) or Methyl-CpG binding proteins (see our work on centipedes and spiders). We aim to better understand this process of host-gene capture in various lineages.