Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition.

Due 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. Prior to 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.

由于数千个种系特异性基因的表达爆发，睾丸拥有所有器官中最多样化和最复杂的转录组。通过分析小鼠雄性种系，我们证明了超增强子（SEs）在全基因组范围内的重组驱动了有丝分裂向减数分裂转变后种系基因表达的爆发。SE重组受两个分子事件调控：通过A - MYB（MYBL1）建立减数分裂特异性SEs，A - MYB是种系基因的关键转录因子；通过SCML2解析有丝分裂增殖细胞中的SEs，SCML2是精子发生特异性基因表达所必需的种系特异性多梳蛋白。在进入减数分裂之前，减数分裂SEs在有丝分裂精原细胞中被预先编程，以确保精子发生的单向分化。我们确定了有丝分裂和减数分裂增强子的关键调控因子，揭示了在体细胞和/或有丝分裂增殖阶段同时激活有丝分裂增强子和抑制减数分裂增强子的分子逻辑。