Owing to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. By analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts in germline gene expression after the mitosis-to-meiosis transition. SE reorganization is regulated by two molecular events: the establishment of meiosis-specific SEs via A-MYB (MYBL1), a key transcription factor for germline genes, and the resolution of SEs in mitotically proliferating cells via SCML2, a germline-specific Polycomb protein required for spermatogenesis-specific gene expression. Before entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia to ensure the unidirectional differentiation of spermatogenesis. We identify key regulatory factors for both mitotic and meiotic enhancers, revealing a molecular logic for the concurrent activation of mitotic enhancers and suppression of meiotic enhancers in the somatic and/or mitotic proliferation phases.

由于数以千计的种系特异性基因表达的爆发，睾丸具有所有器官中最多样化和最复杂的转录组。通过分析小鼠的雄性生殖系，我们证明了在有丝分裂到减数分裂转变后，超级增强子 (SE) 的全基因组重组驱动了生殖系基因表达的爆发。SE重组受两个分子事件的调节：通过种系基因的关键转录因子A-MYB（MYBL1）建立减数分裂特异性SE，以及通过种系特异性Polycomb蛋白SCML2解决有丝分裂增殖细胞中的SE精子发生特异性基因表达所必需的。在进入减数分裂之前，减数分裂 SE 在有丝分裂的精原细胞中被预编程，以确保精子发生的单向分化。