Biology Department, Université de Moncton, Moncton, New-Brunswick, Canada.
Mol Reprod Dev. 2018 Nov;85(11):875-886. doi: 10.1002/mrd.23049. Epub 2018 Aug 29.
Within the seminiferous tubules of the testis, Gja1-encoded connexin43 plays a critical role in intercellular communication between Sertoli cells. These cells nurture, protect and stimulate the developing germ cells and spermatids. SOX transcription factors are known to play an important role in male fertility and sex determination; however, their physiological function and the identity of their target genes in postnatal Sertoli cells remain to be defined. Members of the activating protein-1 (AP-1) family have been shown to regulate Gja1 expression in myometrial and testicular cells and to physically interact with SOX members, suggesting that these transcription factors may regulate its expression within the testis. Hence, we performed co-transfections of expression plasmids encoding SOX4, SOX8, SOX9 and cJUN with different mouse Gja1 promoter/luciferase reporter constructs within TM4 and 15P-1 Sertoli cells. We showed that a functional cooperation between cJUN and SOX8 or SOX9 regulates Gja1 expression and may involve DNA regulatory elements located between -132 and -26 bp. Such synergy relies on the recruitment of cJUN to the -47 base pair (bp) AP-1 DNA regulatory element of the mouse Gja1 promoter. Hence, SOX and AP-1 members cooperate to regulate Gja1 within testicular Sertoli cells.
在睾丸的生精小管中，Gja1 编码的连接蛋白 43 在支持细胞之间的细胞间通讯中发挥关键作用。这些细胞滋养、保护和刺激发育中的精母细胞和精子。SOX 转录因子被认为在男性生育和性别决定中发挥重要作用；然而，它们在生后支持细胞中的生理功能和靶基因的身份仍有待确定。激活蛋白-1（AP-1）家族的成员已被证明可调节子宫和睾丸细胞中 Gja1 的表达，并与 SOX 成员发生物理相互作用，表明这些转录因子可能在睾丸内调节其表达。因此，我们在 TM4 和 15P-1 支持细胞中，将编码 SOX4、SOX8、SOX9 和 cJUN 的表达质粒与不同的小鼠 Gja1 启动子/荧光素酶报告基因构建体进行共转染。我们表明，cJUN 与 SOX8 或 SOX9 之间的功能协同作用调节 Gja1 的表达，并且可能涉及位于-132 和-26bp 之间的 DNA 调节元件。这种协同作用依赖于 cJUN 募集到小鼠 Gja1 启动子的-47 碱基对（bp）AP-1 DNA 调节元件。因此，SOX 和 AP-1 成员在睾丸支持细胞中合作调节 Gja1。
