A Conserved E2F6-Binding Element in Murine Meiosis-Specific Gene Promoters
A Conserved E2F6-Binding Element in Murine Meiosis-Specific Gene Promoters
复制标题
DOI：
10.1095/biolreprod.108.067645
复制
发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Terada, Naohiro
中科院分区：
文献类型：
--
作者：
Kehoe, Sarah M.;Oka, Masahiro;Terada, Naohiro
在配子发生过程中，生殖细胞必须经过减数分裂才能成为有活力的单倍体配子。这一过程的成功完成取决于其蛋白产物在减数分裂中特异性功能的基因的表达。这些基因在减数分裂细胞中表达失败往往导致不育，而在体细胞中异常表达可能导致有丝分裂灾难。调控减数分裂特异性基因及时表达的机制尚未完全阐明。在这里，我们证明了E2F6是E2F转录因子家族的一员，对于抑制体细胞中新发现的减数分裂特异性基因Slc25a31（也称为Ant4， Aac4）是必不可少的。这一发现，连同之前的研究，促使我们研究E2F6在减数分裂特异性基因的一般调控中的作用。有趣的是，核心e2f6结合元件（TCCCGC）在24个减数分裂特异性基因中的19个（79.2%）的近端启动子区域高度保守。这明显高于所有小鼠基因启动子的频率（15.4%）。在缺乏E2F6的情况下，体细胞中只有一部分减数分裂特异性基因被抑制。然而，内源性E2F6结合到这些减数分裂特异性基因的启动子上，无论它们在体细胞中是否需要E2F6来抑制它们。此外，E2F6过表达能够降低它们的转录。这些发现表明E2F6具有广泛的结合和调节减数分裂特异性基因群体的能力。
During gametogenesis, germ cells must undergo meiosis in order to become viable haploid gametes. Successful completion of this process is dependent upon the expression of genes whose protein products function specifically in meiosis. Failure to express these genes in meiotic cells often results in infertility, whereas aberrant expression in somatic cells may lead to mitotic catastrophe. The mechanisms responsible for regulating the timely expression of meiosis-specific genes have not been fully elucidated. Here we demonstrate that E2F6, a member of the E2F family of transcription factors, is essential for the repression of the newly identified meiosis-specific gene, Slc25a31 (also known as Ant4, Aac4), in somatic cells. This discovery, along with previous studies, prompted us to investigate the role of E2F6 in the regulation of meiosis-specific genes in general. Interestingly, the core E2F6-binding element (TCCCGC) was highly conserved in the proximal promoter regions of 19 out of 24 (79.2%) meiosis-specific genes. This was significantly higher than the frequency found in the promoters of all mouse genes (15.4%). In the absence of E2F6, only a portion of these meiosis-specific genes was derepressed in somatic cells. However, endogenous E2F6 bound to the promoters of these meiosis-specific genes regardless of whether they required E2F6 for their repression in somatic cells. Further, E2F6 overexpression was capable of reducing their transcription. These findings indicate that E2F6 possesses a broad ability to bind to and regulate the meiosis-specific gene population.