Genome-wide epigenetic reprogramming during chick embryonic development

In mice, genome-wide DNA methylation is actively erased at the onset of fertilisation, followed by remethylation in epiblasts after implantation, leading to inactive chromatin formation as a preliminary step to somatic cell differentiation, and then demethylation again during primitive streak formation and the determination of primordial germ cells (PGCs). This sequence of DNA methylation changes is accompanied by dynamic epigenetic reprogramming, including nuclear structure, histone modification, and intranuclear re-localisation of chromosomes, during totipotency acquisition of the fertilised egg and germline development. Here we show that in the avian strain White Leghorn of Gallus gallus domesticus, global reprogramming of DNA methylation and histone modifications, as seen in mice, is induced during primitive streak formation but then reaches an almost basal state in somatic cells during later embryogenesis unlike mice. Avian chromosomes are subdivided into large and genetically less functioning macrochromosomes (MACs) and gene-rich microchromosomes (MICs), of which remarkable karyotypic composition is evolutionarily conserved from cartilaginous fish to reptiles. We found that these MACs undergo reprogramming that involves particularly active DNA demethylation and removal of trimethylation at lysine 9 of histone H3, leading to activation of the MAC-linked HOXA and HOXD gene clusters that control morphogenesis. We show here that the erasure of genome-wide epigenetics may not only have an important function to initiate differentiation into three germ layers via primitive streak formation, as seen in mice but may also provide a basis for the acquisition of new epigenetics required to regulate morphogenesis during late chicken embryonic development. Overall design: ChIP-seq data for H3K9me3, H3K27me3, and H3K4me2 from HH27 chicken embryos and DT40 cells