GSE109344
Reprogramming of meiotic chromatin architecture during primate spermatogenesis
Chromatin organization undergoes drastic reprogramming during gametogenesis . However, the three-dimensional chromatin structure and its reprogramming remain largely unknown, with even less known for primates. Here, by using a low-input Hi-C method we developed recently, we examined re-organization of 3D chromatin architecture during spermatogenesis in rhesus monkey (Macaca mulatta). Interestingly, we found that topologically associating domains (TADs) are partially dissolved in spermatogonia and are further depleted at the pachytene stage, before they gradually become consolidated in round spermatids and mature sperm. Strikingly, in local regions, pachytene chromatin is uniquely characterized by highly refined compartments that alternate between transcribing regions (Refined-A) and non-transcribed regions (Refined-B). Refined A/B occurs genomewide except for the X chromosome, which is inactivated at this stage. Interestingly, such chromatin organization remains intact upon transcription inhibition but is disrupted in spermatocytes deficient in SYCP2, a core component of synaptonemal complex. Strikingly, this is accompanied by the restoration of TADs in these mutant cells, suggesting that synaptonemal complex may restrict TADs and permit the emergence of strong local compartments. Taken together, these data reveal extensive reprogramming of higher-order meiotic chromatin architecture during mammalian gametogenesis. Overall design: Rhesus monkey spermatogonia (SPA), pachytene spermatocytes (PAC), round spermatids (RS) and sperm were obtained, together with fibroblast as control. Mouse PAC were treated with amantin to test the effect of trancription inhibition. Sycp2 KO or Top6bl KO mouse PAC-like cells were used to explore the contribution of synaptonemal complex towards higher order chromatin organization. HiC, STEM-seq and RNA-seq were performed in these cells at various stages during spermatogenesis.