In most mammals the major site of sex hormone-binding globulin (SHBG) synthesis is the liver wherefrom it is secreted into the bloodstream and is the primary determinant of sex steroid access to target tissues. The minor site of SHBG synthesis is the testis and in lower mammals testicular SHBG has long been known to be synthesized and secreted by Sertoli cells. However, human testicular is expressed in developing germ cells from an upstream alternative promoter (altP-). Transcripts arising from this region comprise an alternative first exon (1A) with the resultant protein confined to the acrosomal compartment of the mature spermatozoa. I have dissected the regulatory components of the alternative promoter and identified motifs that are required for optimal transcriptional activity from this region. Transcriptional activity is driven by two CACCC elements that appear to be functionally redundant. The transcription factor KLF4 interacts with promoter the region spanning these elements . Knockdown of results in decreased altP- activity, while overexpression relieves the effects of knockdown. Based on their shared patterns of expression , I conclude that KLF4 is a transcriptional regulator of in male germ cells.

中文翻译：

---

KLF4 对替代性激素结合球蛋白启动子的转录调控

在大多数哺乳动物中，性激素结合球蛋白（SHBG）合成的主要部位是肝脏，从那里它被分泌到血液中，并且是性类固醇进入靶组织的主要决定因素。SHBG 合成的次要部位是睾丸，长期以来已知低等哺乳动物的睾丸 SHBG 由支持细胞合成和分泌。然而，人类睾丸在发育中的生殖细胞中由上游替代启动子（altP-）表达。该区域产生的转录本包含一个替代的第一外显子 (1A)，所得蛋白质局限于成熟精子的顶体区室。我已经剖析了替代启动子的调控组件，并确定了该区域最佳转录活性所需的基序。转录活动由两个 CACCC 元件驱动，这两个元件在功能上似乎是冗余的。转录因子 KLF4 与跨越这些元件的区域的启动子相互作用。敲低会导致 altP- 活性降低，而过表达会减轻敲低的影响。根据它们共同的表达模式，我得出结论，KLF4 是雄性生殖细胞中的转录调节因子。