Seminar: Dr. Lan Xu

Dr. Lan Xu,  Postdoctoral Researcher, School of Biological and Behavioral Sciences, Queen Mary University of London, London, United Kingdom

Title: The role and inheritance of gene body methylation in a cnidarian

Abstract: DNA methylation is commonly associated with gene silencing, yet in invertebrates most methylation accumulates in actively transcribed gene bodies, posing a longstanding paradox. Gene body methylation (gbM) has been hypothesized to stabilize gene expression, suppress intragenic transcription, or mediate environmental responses, yet direct experimental evidence for these functions remains limited. Here, we use the cnidarian Nematostella vectensis as a model to demonstrate that loss of DNA
methylation results in viable embryos with limited effects on gene expression. Instead, methylation depletion leads to extensive aberrant chromatin accessibility and spurious transcriptional initiation, particularly associated to transposable elements within normally
methylated gene bodies. This supports a model in which gbM suppresses cryptic regulatory activity in broadly transcribed regions. We further show that abnormal methylation patterns are partially restored in the germline, with recovery biased toward transcriptionally active regions and exclusion from repressive chromatin. Moreover, we show that abnormal methylation states are inherited into the next generation, demonstrating an absence of epigenetic reprogramming. Our findings reveal a conserved protective role for gbM, demonstrate the capacity for transgenerational epigenetic inheritance, and highlight potential of DNA methylation as a regulatory substrate for natural selection. Strikingly, we also found that following demethylation, some animals that would normally develop as either males or females, instead developed as hermaphrodites. This unexpected finding has opened a new avenue to investigate how epigenetic mechanisms regulate and potentially reprogramme sex fate in an animal that lacks sex chromosomes.