Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, School of Life Sciences, THU-PKU Center for Life Science, Tsinghua University, Beijing 100084, China.
State Key Laboratory of Reproductive Medicine (SKLRM), Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Mol Cell. 2019 Feb 7;73(3):547-561.e6. doi: 10.1016/j.molcel.2018.11.019.
Chromatin organization undergoes drastic reconfiguration during gametogenesis. However, the molecular reprogramming of three-dimensional chromatin structure in this process remains poorly understood for mammals, including primates. Here, we examined three-dimensional chromatin architecture during spermatogenesis in rhesus monkey using low-input Hi-C. Interestingly, we found that topologically associating domains (TADs) undergo dissolution and reestablishment in spermatogenesis. Strikingly, pachytene spermatocytes, where synapsis occurs, are strongly depleted for TADs despite their active transcription state but uniquely show highly refined local compartments that alternate between transcribing and non-transcribing regions (refined-A/B). Importantly, such chromatin organization is conserved in mouse, where it remains largely intact upon transcription inhibition. Instead, it is attenuated in mutant spermatocytes, where the synaptonemal complex failed to be established. Intriguingly, this is accompanied by the restoration of TADs, suggesting that the synaptonemal complex may restrict TADs and promote local compartments. Thus, these data revealed extensive reprogramming of higher-order meiotic chromatin architecture during mammalian gametogenesis.
染色质组织在配子发生过程中经历剧烈的重新配置。然而，包括灵长类动物在内的哺乳动物这一过程中三维染色质结构的分子重编程仍知之甚少。在这里，我们使用低投入的 Hi-C 技术研究了食蟹猴精子发生过程中的三维染色质结构。有趣的是，我们发现拓扑关联域（TAD）在精子发生过程中会溶解和重新建立。引人注目的是，尽管精母细胞处于活跃转录状态，但它们的 TAD 明显缺失，尽管如此，它们仍然表现出高度精细的局部隔室，这些隔室在转录和非转录区域之间交替（精细-A/B）。重要的是，这种染色质组织在小鼠中是保守的，在转录抑制后仍然基本完整。相反，在联会复合体未能建立的突变型精母细胞中，这种组织会减弱。有趣的是，这伴随着 TAD 的恢复，表明联会复合体可能限制 TAD 并促进局部隔室。因此，这些数据揭示了哺乳动物配子发生过程中高级减数分裂染色质结构的广泛重编程。
