Abstract
Human sperm and oocytes carry highly distinct DNA methylation landscapes, yet parental DNA methylation ultimately converges to a largely equivalent state, raising the question of when and how the allelic DNA methylome is reprogrammed toward convergence. Here, we present an integrated allelic analysis of DNA methylation and transcriptome dynamics throughout human pre- to peri-implantation development, a stage that lays the foundation for future development. We find that oocyte-specific hypermethylated regions retain maternal-biased DNA methylation asymmetry throughout early development, whereas paternal hypermethylation at sperm-specific regions is erased after fertilization and re-established during peri-implantation. Whole-genome parental DNA methylation levels converge across all lineages at embryonic days 8 to 12, prior to gastrulation, although the timing of this equilibrium differs among genomic elements. Notably, a subset of transposable elements, including SVAs and LTR12 elements, remains persistently maternally hypermethylated. Finally, we identify parent-of-origin-biased genes involved in early human embryonic development and find that these genes are enriched for dosage-sensitive genes. We further show that epiblast-specific parental expression bias is associated with genes implicated in neurodevelopmental disorders. These findings highlight the developmental and clinical relevance of allele-specific DNA methylation and transcription regulation during the earliest stages of human development.