Bacteria contain conserved mechanisms to control the intracellular levels of metal ions. Metalloregulatory transcription factors bind metal cations and play a central role in regulating gene expression of metal transporters. Often, these transcription factors regulate transcription by binding to a specific DNA sequence in the promoter region of target genes. Understanding the preferred DNA‐binding sequence for transcriptional regulators can help uncover novel gene targets and provide insight into the biological role of the transcription factor in the host organism. Here, we identify consensus DNA‐binding sequences and subsequent transcription regulatory networks for two metalloregulators from the ferric uptake regulator (FUR) and diphtheria toxin repressor (DtxR) superfamilies in Thermus thermophilus HB8. By homology search, we classify the DtxR homolog as a manganese‐specific, MntR (TtMntR), and the FUR homolog as a peroxide‐sensing, PerR (TtPerR). Both transcription factors repress separate ZIP transporter genes in vivo, and TtPerR acts as a bifunctional transcription regulator by activating the expression of ferric and hemin transport systems. We show TtPerR and TtMntR bind DNA in the presence of manganese in vitro and in vivo; however, TtPerR is unable to bind DNA in the presence of iron, likely due to iron‐mediated histidine oxidation. Unlike canonical PerR homologs, TtPerR does not appear to contribute to peroxide detoxification. Instead, the TtPerR regulon and DNA binding sequence are more reminiscent of Fur or Mur homologs. Collectively, these results highlight the similarities and differences between two metalloregulatory superfamilies and underscore the interplay of manganese and iron in transcription factor regulation.

中文翻译：

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嗜热栖热菌 HB8 中 MntR 和 PerR 的锰依赖性转录调控

细菌含有控制细胞内金属离子水平的保守机制。金属调节转录因子结合金属阳离子，在调节金属转运蛋白的基因表达中发挥核心作用。通常，这些转录因子通过与靶基因启动子区域的特定 DNA 序列结合来调节转录。了解转录调节因子的首选 DNA 结合序列有助于发现新的基因靶标，并深入了解转录因子在宿主生物体中的生物学作用。在这里，我们确定了来自铁摄取调节子（FUR）和白喉毒素抑制子（DtxR）超家族的两个金属调节子的共有DNA结合序列和随后的转录调节网络嗜热栖热菌HB8。通过同源搜索，我们将 DtxR 同源物分类为锰特异性 MntR（ttMntR)，以及作为过氧化物传感的 FUR 同系物 PerR (tt佩尔）。两种转录因子在体内分别抑制 ZIP 转运蛋白基因，并且ttPerR 通过激活铁和血红素转运系统的表达充当双功能转录调节剂。我们展示tt佩尔和tt在锰存在的情况下，MntR 在体内和体外结合 DNA；然而，ttPerR 在铁存在的情况下无法结合 DNA，可能是由于铁介导的组氨酸氧化。与典型的 PerR 同系物不同，ttPerR 似乎对过氧化物解毒没有贡献。相反，ttPerR 调节子和 DNA 结合序列更让人想起 Fur 或 Mur 同源物。总的来说，这些结果突出了两个金属调节超家族之间的相似性和差异，并强调了锰和铁在转录因子调节中的相互作用。