Vernet Nadège, Mahadevaiah Shantha K, Yamauchi Yasuhiro, Decarpentrie Fanny, Mitchell Michael J, Ward Monika A, Burgoyne Paul S
MRC National Institute for Medical Research, London, United Kingdom; Department of functional genomics and cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
MRC National Institute for Medical Research, London, United Kingdom.
PLoS Genet. 2014 Jun 26;10(6):e1004444. doi: 10.1371/journal.pgen.1004444. eCollection 2014 Jun.
Mouse Zfy1 and Zfy2 encode zinc finger transcription factors that map to the short arm of the Y chromosome (Yp). They have previously been shown to promote meiotic quality control during pachytene (Zfy1 and Zfy2) and at the first meiotic metaphase (Zfy2). However, from these previous studies additional roles for genes encoded on Yp during meiotic progression were inferred. In order to identify these genes and investigate their function in later stages of meiosis, we created three models with diminishing Yp and Zfy gene complements (but lacking the Y-long-arm). Since the Y-long-arm mediates pairing and exchange with the X via their pseudoautosomal regions (PARs) we added a minute PAR-bearing X chromosome derivative to enable formation of a sex bivalent, thus avoiding Zfy2-mediated meiotic metaphase I (MI) checkpoint responses to the unpaired (univalent) X chromosome. Using these models we obtained definitive evidence that genetic information on Yp promotes meiosis II, and by transgene addition identified Zfy1 and Zfy2 as the genes responsible. Zfy2 was substantially more effective and proved to have a much more potent transactivation domain than Zfy1. We previously established that only Zfy2 is required for the robust apoptotic elimination of MI spermatocytes in response to a univalent X; the finding that both genes potentiate meiosis II led us to ask whether there was de novo Zfy1 and Zfy2 transcription in the interphase between meiosis I and meiosis II, and this proved to be the case. X-encoded Zfx was also expressed at this stage and Zfx over-expression also potentiated meiosis II. An interphase between the meiotic divisions is male-specific and we previously hypothesised that this allows meiosis II critical X and Y gene reactivation following sex chromosome silencing in meiotic prophase. The interphase transcription and meiosis II function of Zfx, Zfy1 and Zfy2 validate this hypothesis.
小鼠的Zfy1和Zfy2基因编码锌指转录因子，定位于Y染色体短臂（Yp）。先前研究表明，它们在粗线期（Zfy1和Zfy2）以及第一次减数分裂中期（Zfy2）促进减数分裂质量控制。然而，从这些先前的研究中可以推断出Yp上编码的基因在减数分裂进程中还有其他作用。为了鉴定这些基因并研究它们在减数分裂后期的功能，我们构建了三个Yp和Zfy基因互补逐渐减少的模型（但缺少Y染色体长臂）。由于Y染色体长臂通过其假常染色体区域（PARs）介导与X染色体的配对和交换，我们添加了一个微小的携带PAR的X染色体衍生物，以促成性二价体的形成，从而避免Zfy2介导的减数分裂中期I（MI）对未配对（单价）X染色体的检查点反应。利用这些模型，我们获得了确凿的证据，证明Yp上的遗传信息促进减数分裂II，并通过添加转基因确定Zfy1和Zfy2是负责的基因。Zfy2的效果显著更强，并且证明其具有比Zfy1更强有力的反式激活结构域。我们先前确定，对于单价X染色体，只有Zfy2是MI精母细胞强大凋亡消除所必需的；这两个基因都增强减数分裂II的发现促使我们询问在减数分裂I和减数分裂II之间的间期是否有Zfy1和Zfy2的从头转录，事实证明确实如此。X染色体编码的Zfx在这个阶段也有表达，并且Zfx的过表达也增强了减数分裂II。减数分裂各阶段之间的间期是雄性特有的，我们先前假设这允许在减数分裂前期性染色体沉默后，减数分裂II关键的X和Y基因重新激活。Zfx、Zfy1和Zfy2的间期转录以及减数分裂II功能验证了这一假设。
