Three-dimensional genome structures of single mammalian sperm [scHi-C]

The three-dimensional (3D) organization of chromosomes is crucial for packaging a large mammalian genome into a confined nucleus and ensuring proper nuclear functions in somatic cells. However, the packaging of the much more condensed sperm genome is fundamentally different and not as well understood. In this study, we resolved the 3D whole-genome structures of a single mammalian sperm cell using an enhanced chromosome conformation capture assay. The reconstructed genome structures accurately delineate the species-specific nuclear morphologies for both human and mouse sperm. We discovered that sperm genomes are divided into chromosomal territories and A/B compartments, similarly as somatic cells. However, neither human nor mouse sperm chromosomes contain topologically associating domains or chromatin loops. These results suggest that the fine-scale chromosomal organization of mammalian sperm fundamentally differs from that of somatic cells. Develop a new optimized Hi-C experimental approach to analyze the three-dimensional architecture of mouse and human sperm nuclei.