Oral Presentation 45th Lorne Genome Conference 2024

Extensive DNA methylome rearrangement during early lamprey embryogenesis (#51)

Allegra Angeloni 1 2 , Skye Fissette 3 , Deniz Kaya 4 , Jillian M Hammond 1 5 , Hasindu Gamaarachchi 1 5 6 , Ira W Deveson 1 5 7 , Robert J Klose 4 , Weiming Li 3 , Xiaotian Zhang 8 9 , Ozren Bogdanovic 1 2 10
  1. Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, NSW, Australia
  3. Department of Fisheries and Wildlife, Michigan State University, East Lansing, Michigan, United States
  4. Department of Biochemistry, University of Oxford, Oxford, United Kingdom
  5. Centre for Population Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia
  6. School of Computer Science and Engineering, UNSW, Sydney, NSW, Australia
  7. Faculty of Medicine, UNSW, Sydney, NSW, Australia
  8. Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, United States
  9. University of Texas Health Science Center, University of Texas, Houston, Texas, United States
  10. Centro Andaluz de Biología del Desarrollo, Seville, Spain

DNA methylation (5-methylcytosine, 5mC) is an epigenetic mark that plays a crucial role in defining cell fate. After fertilization, 5mC patterns inherited from parental gametes are reprogrammed in the early embryo to establish a 5mC state compatible with totipotency. Intriguingly, 5mC dynamics are varied across vertebrate species, and it remains unclear how functionally conserved such strategies are, and what their biological function is. The sea lamprey Petromyzon marinus is an extant jawless fish that, as a basal vertebrate, serves as a valuable model for understanding the evolutionary origins of 5mC reprogramming. Unlike most other vertebrate genomes that are hypermethylated, lamprey displays high levels of 5mC heterogeneity between individual cells. This study aims to explore whether this unique 5mC configuration is compatible with developmental reprogramming, to gain deeper insights into the evolutionary dynamics of 5mC function.

To achieve this, we produced high resolution epigenome maps of lamprey development, employing whole-genome bisulfite sequencing, biochemical identification of non-methylated DNA (BioCAP) and Nanopore sequencing of germline, embryonic, and somatic tissues. We discovered that the early embryo adopts a sperm-like DNA methylome before the onset of zygotic gene expression, an epigenetic remodelling process also conserved in zebrafish and medaka. Importantly, most of this reprogramming occurs over partially methylated domains that cover ~30% of the genome, representing a relatively large-scale and lineage-specific reprogramming event. In addition, the lamprey genome undergoes programmed DNA loss during early embryogenesis, in which genomic DNA present in the germline is physically eliminated in somatic lineages. We found that eliminated sequences are hypermethylated in the germline genome, where 5mC is possibly implicated in their removal. 

Our findings demonstrate that the lamprey genome undergoes extensive 5mC remodelling predominantly associated with partially methylated DNA. This work provides new insights into the evolutionary origins of complex gene regulatory states that characterize vertebrate development.