Duke University, Department of Biology and Institute for Genome Sciences and Policy, Center for Systems Biology, Durham, NC 27708, USA.
Nucleic Acids Res. 2011 Apr;39(7):2519-33. doi: 10.1093/nar/gkq1211. Epub 2010 Nov 24.
Because iron toxicity and deficiency are equally life threatening, maintaining intracellular iron levels within a narrow optimal range is critical for nearly all known organisms. However, regulatory mechanisms that establish homeostasis are not well understood in organisms that dwell in environments at the extremes of pH, temperature, and salinity. Under conditions of limited iron, the extremophile Halobacterium salinarum, a salt-loving archaeon, mounts a specific response to scavenge iron for growth. We have identified and characterized the role of two transcription factors (TFs), Idr1 and Idr2, in regulating this important response. An integrated systems analysis of TF knockout gene expression profiles and genome-wide binding locations in the presence and absence of iron has revealed that these TFs operate collaboratively to maintain iron homeostasis. In the presence of iron, Idr1 and Idr2 bind near each other at 24 loci in the genome, where they are both required to repress some genes. By contrast, Idr1 and Idr2 are both necessary to activate other genes in a putative a feed forward loop. Even at loci bound independently, the two TFs target different genes with similar functions in iron homeostasis. We discuss conserved and unique features of the Idr1-Idr2 system in the context of similar systems in organisms from other domains of life.
由于铁毒性和缺铁同样会危及生命，因此维持细胞内铁水平在狭窄的最佳范围内对于几乎所有已知的生物都至关重要。然而，在栖息于 pH 值、温度和盐度极端环境的生物中，建立体内平衡的调节机制还不是很清楚。在铁有限的情况下，嗜盐古菌盐生盐杆菌会对铁进行专门的掠夺，以促进生长。我们已经确定并描述了两个转录因子（TFs），Idr1 和 Idr2，在调节这一重要反应中的作用。在存在和不存在铁的情况下，对 TF 敲除基因表达谱和全基因组结合位置进行综合系统分析表明，这些 TF 协同作用以维持铁的体内平衡。在铁存在的情况下，Idr1 和 Idr2 在基因组中的 24 个位置相互靠近结合，在这些位置，它们都需要抑制一些基因。相比之下，Idr1 和 Idr2 都需要激活其他基因，形成一个潜在的正反馈回路。即使在独立结合的位置，两个 TF 也会针对具有相似功能的不同基因进行铁稳态调控。我们将 Idr1-Idr2 系统的保守和独特特征放在来自生命其他领域的生物的类似系统的背景下进行讨论。
