Attenuated chromatin compartmentalization in meiosis and its maturation in sperm development

Germ cells manifest a unique gene expression program and regain totipotency in the zygote. Here, we perform Hi-C analysis to examine 3D chromatin organization in male germ cells during spermatogenesis. We show that the highly compartmentalized 3D chromatin organization characteristic of interphase nuclei is attenuated in meiotic prophase. Meiotic prophase is predominated by short-range intrachromosomal interactions that represent a condensed form akin to that of mitotic chromosomes. However, unlike mitotic chromosomes, meiotic chromosomes display weak genomic compartmentalization, weak topologically associating domains, and localized point interactions in prophase. In postmeiotic round spermatids, genomic compartmentalization increases and gives rise to the strong compartmentalization seen in mature sperm. The X chromosome lacks domain organization during meiotic sex-chromosome inactivation. We propose that male meiosis occurs amid global reprogramming of 3D chromatin organization and that strengthening of chromatin compartmentalization takes place in spermiogenesis to prepare the next generation of life. Examination of meiotic pachytene spermatocytes (PS; 2 biological replicates) and postmeiotic round spermatids (RS; 2 biological replicates) via Hi-C, performed alongside third-party reanalyses of the following published reference datasets: sperm (PMID 28178516, GSE79230; 2 biological replicates) and embryonic stem cells (ESC; PMID 24185094, GSE48592; 2 biological replicates), non-synchronized human foreskin fibroblasts (HFF1 non-synchronized; PMID 24200812, ArrayExpress E-MTAB-1948; 1 biological sample), synchronized prometaphase mitosis human foreskin fibroblasts (HFF1 mitosis; PMID 24200812, ArrayExpress E-MTAB-1948; 1 biological sample), and metaphase meiosis II oocytes (MII oocytes; PMID 28703188, GSE82185; 2 biological replicates).