Basic helix-loop-helix proteins can act at the E-box within the serum response element of the c-fos promoter to influence hormone-induced promoter activation in Sertoli cells.
Basic helix-loop-helix proteins can act at the E-box within the serum response element of the c-fos promoter to influence hormone-induced promoter activation in Sertoli cells.
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DOI：
10.1210/mend.13.5.0271
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发表时间：
1999-05
影响因子：
--
通讯作者：
Jaideep Chaudhary;Michael K. Skinner
中科院分区：
文献类型：
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作者：
Jaideep Chaudhary;Michael K. Skinner
支持细胞是成人中维持精子发生过程所需的终末分化睾丸细胞。此前，碱性螺旋-环-螺旋 (bHLH) 因子和 c-fos 已被证明可以影响支持细胞的分化功能。支持细胞分化的诱导似乎涉及 c-fos 启动子的血清反应元件 (SRE)，以激活 c-fos 和调节下游支持细胞分化基因（例如转铁蛋白表达）的中间 bHLH 因子。 c-fos 启动子的 SRE 受血清反应因子 (SRF) 的影响。有趣的是，SRE 内存在 E-box 核苷酸序列。 bHLH 蛋白通过 E-box 元件发挥作用，目前的研究调查了 bHLH 蛋白可能直接影响 c-fos 启动子的 SRE 的可能性。发现支持细胞中c-fos启动子的激活因抑制性HLH蛋白Id的过表达而受到抑制。对c-fos启动子内主要反应元件的分析表明，Id的表达特异性抑制支持细胞中SRE的激活，并且没有测试其他元件。 SRE E-box 的突变也抑制了 SRE 的激活，表明 bHLH 蛋白在调节支持细胞中的 SRE 活性中具有直接作用。相反，含有突变E-box的SRE的激活与对照基质细胞中的野生型SRE相当。使用支持细胞核提取物对 SRE 寡核苷酸凝胶迁移率变化分析进行分析，证明存在 SRF 和普遍表达的 bHLH 蛋白 E12/E47。相反，使用对照基质细胞核提取物进行的 SRE 寡核苷酸凝胶迁移中没有检测到 E12/E47。观察结果表明 E12/E47 与 SRE 的结合可能是细胞特异性事件。 SRF 和 bHLH 蛋白似乎与 SRE 结合并激活支持细胞中的 c-fos 启动子。观察结果表明，bHLH 蛋白可以与 c-fos 启动子的 SRE 相互作用，从而影响激素诱导的启动子激活。这些核转录因子之间的串扰似乎有助于控制支持细胞的分化功能。
The Sertoli cell is a terminally differentiated testicular cell in the adult required to maintain the process of spermatogenesis. Previously basic helix-loop-helix (bHLH) factors and c-fos have been shown to influence Sertoli cell-differentiated functions. The induction of Sertoli cell differentiation appears to involve the serum response element (SRE) of the c-fos promoter to activate c-fos and intermediate bHLH factor(s) that regulate down-stream Sertoli cell-differentiated genes (e.g. transferrin expression). The SRE of the c-fos promoter is influenced through the serum response factor (SRF). Interestingly, an E-box nucleotide sequence is present within the SRE. bHLH proteins act through E-box elements, and the current study investigates the possibility that bHLH proteins may directly influence the SRE of the c-fos promoter. The activation of the c-fos promoter in Sertoli cells was found to be inhibited with the overexpression of the inhibitory HLH protein Id. Analysis of major response elements within the c-fos promoter demonstrated that the expression of Id specifically inhibited the activation of SRE in Sertoli cells and no other elements tested. Mutations in the E-box of the SRE also inhibited the activation of SRE, suggesting the direct role of bHLH proteins in regulating SRE activity in Sertoli cells. In contrast, the activation of SRE containing a mutated E-box was comparable to wild-type SRE in control stromal cells. Analysis of SRE oligonucleotide gel mobility shift assays with nuclear extracts from Sertoli cells demonstrated the presence of both the SRF and the ubiquitously expressed bHLH protein E12/E47. In contrast, no E12/E47 was detected in the SRE oligonucleotide gel shift using control stromal cell nuclear extracts. Observations suggest the binding of E12/E47 to SRE may be a cell-specific event. The SRF and bHLH proteins appear to bind to the SRE and activate the c-fos promoter in Sertoli cells. Observations provide evidence that a bHLH protein can interact with the SRE of the c-fos promoter to influence hormone-induced promoter activation. Cross-talk between these nuclear transcription factors appears to be instrumental in the control of Sertoli cell-differentiated functions.