Past Issue

Volume 9, Supplement 1, Summer 2015 (Presented at 16th Congress on Reproductive Biomedicine and 10th Royan Nursing and Midwifery Seminar) Pages: 27-27

O-5: Reprogramming of Paternal DNA Methylome during Spermiogenesis


Background
Chromatin of male and female gametes undergoes a number of reprogramming events during the transition from germ cell to embryonic developmental programs in the zygote. This process involves reorganisation of the patterns of 5-methylcytosine (5mC), a DNA modification associated with regulation of gene activity. Notably, both maternal and paternal genomes undergo Tet3-dependent oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in one-cell embryos. Although the precise biological functions of these oxidised forms of 5mC remain elusive, they may play specific roles in active demethylation and transcriptional regulation.
Materials and methods
Here we present the results of genome-scale analysis of 5mC/5hmC/5caC distributions in round spermatids and spermatozoa and demonstrate that reprogramming of the paternal methylome begins during spermatid maturation.
Results
We show that patterns of 5caC genomic distribution are highly dynamic during spermiogenesis. Whereas 5caC is eliminated from LINE1 retroposons and transcriptionally active spermiogenesis-specific genes during spermatid maturation, it is simultaneously accumulated at promoter regions and introns of the genes involved in embryo development. Importantly, a large fraction of 5caC-enriched genes also retain nucleosomes marked with bivalent histone modifications in spermatozoa chromatin.
Conclusion
Our results suggest that embryonic patterns of DNA modifications are prearranged during spermatid maturation and imply a role for 5caC in poising the activity of developmental genes in mammalian embryogenesis.