Transcriptional regulation of spatiotemporal gene expression within the seminiferous epithelium: Mouse Acrv1 gene as a model.
Transcriptional regulation of spatiotemporal gene expression within the seminiferous epithelium: Mouse Acrv1 gene as a model.
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生精上皮内时空基因表达的转录调控：以小鼠 Acrv1 基因为模型。
DOI：
10.1111/andr.13410
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发表时间：
2023
期刊：
影响因子：
4.5
通讯作者：
Reddi,PrabhakaraP
中科院分区：
文献类型：
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作者：
Reddi,PrabhakaraP
精原细胞、精母细胞和圆形精子细胞特有的分化标志物的精确时空表达点缀着精子发生并确保其完成。例如，编码联会复合体或顶体或鞭毛的基因通常以发育阶段和生殖细胞特有的方式顺序表达。但是，调控生精上皮内基因表达时空顺序的转录机制还知之甚少。以编码顶体蛋白SP-10的圆形精子细胞特异性基因Acrv1为模型，我们了解到(1)近端启动子本身包含所有必要的顺式调控序列，(2)绝缘体阻止睾丸特异基因在体细胞中的表达，(3)RNA II聚合酶加载在Acrv1启动子上但在精母细胞中暂停，从而确保圆形精子细胞的精确转录延长，以及(4)43千道尔顿的转录抑制物结合蛋白(TDP-43)在维持精母细胞的暂停状态中起作用。尽管Acrv1增强子元件已被缩小到50kb，并显示其与47kDa睾丸丰富的核蛋白的结合，但负责激活圆形精子细胞特异性转录的假定转录因子的身份仍然难以确定。人类男性不育症是特发性的，治疗选择有限。了解精子发生的转录调控有可能导致未来的男性不育治疗。
Precise spatiotemporal expression of cohorts of differentiation markers unique to spermatogonia, spermatocytes, and round spermatids punctuates spermatogenesis and ensures its completion. For example, genes coding for the synaptonemal complex or the acrosome or flagellum are expressed sequentially in a developmental stage‐ and germ cell‐specific manner. But the transcriptional mechanisms governing the spatiotemporal order of gene expression within the seminiferous epithelium are poorly understood. Using the round spermatid‐specificAcrv1gene, which codes for the acrosomal protein SP‐10 as a model, we learned that (1) the proximal promoter itself contains all the necessary cis‐regulatory sequences, (2) an insulator prevents somatic cell expression of the testis‐specific gene, (3) RNA II polymerase is loaded on theAcrv1promoter but paused in spermatocytes, thus ensuring precise transcriptional elongation in round spermatids, and that (4) a transcriptional repressor binding protein of 43 kilodaltons (TDP‐43) plays a role in maintaining the paused state in spermatocytes. Although the Acrv1 enhancer element has been narrowed down to 50 bp and its binding to a 47 kDa testis‐abundant nuclear protein shown, the identity of the putative transcription factor responsible for activation of round spermatid‐specific transcription remains elusive. Human male infertility is idiopathic with limited treatment options. Understanding transcriptional regulation of spermatogenesis has the potential to lead to future therapies for male infertility.