Conserved and divergent DNA methylation features of extraembryonic tissues between human, mouse and chicken

Background: The first cell fate decisions in embryogenesis give rise to extraembryonic tissues, such as the yolk sac and placenta, which are essential for embryo survival. In mammals, extraembryonic cell types arising from these first lineage decisions show distinct DNA methylation patterning, including large partially methylated domains, gene body methylation and accumulation across developmental CpG island (CGI) promoters. Analysis of extraembryonic membranes beyond mammalian species has been limited. Using bisulphite-seq and RNA-seq, we comparatively define these epigenetic characteristics of extraembryonic membranes in both mouse and human. We then tested whether these features are conserved in the chicken extraembryonic membranes (EEMs) including the yolk sac, chorion and chorioallantoic membrane (CAM). Results: Transcriptomic analysis revealed that embryonic day (E)4 yolk sac/chorion and E14 CAM express similar marker genes to the mouse chorionic trophoblast, supporting that the chicken chorionic ectoderm shares a ‘trophoblast-like’ cell identity. We find that partially methylated domains and transcription-linked gene body methylation patterning are highly conserved between mouse and human proliferative multipotent trophoblast cells but were not evident in the chicken EEMs. However, we find that methylation of CGIs associated with developmental genes was a conserved feature of mouse, human and chicken EEMs. Conclusions: These findings support that features of the extraembryonic DNA methylation landscape have distinct underlying mechanisms. We find that only one feature is conserved across extant amniotes, suggesting distinct evolutionary pressures associated with different features of EEM epigenetic patterning.