Revisiting Fur Regulon Leads to a Comprehensive Understanding of Iron and Fur Regulation

• Published in: International journal of molecular sciences 2023-05, Vol.24 (10), p.9078
• Main Authors: Hou, Chaofan, Liu, Lin, Ju, Xian, Xiao, Yunzhu, Li, Bingyu, You, Conghui
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding sites; carbon metabolism; E coli; Enzymes; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli K12 - genetics; ferric-uptake regulator; Gene expression; Gene Expression Regulation, Bacterial; Gene silencing; Genes; Hemostasis; Hemostatics; Iron; Iron - metabolism; Metabolism; motility; Physiological aspects; Proteins; Regulations; Regulon - genetics; Repressor Proteins - genetics; Repressor Proteins - metabolism; Respiration; RNA polymerase; Transcriptomics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24109078

Iron is an essential element because it functions as a cofactor of many enzymes, but excess iron causes cell damage. Iron hemostasis in was transcriptionally maintained by the ferric uptake regulator (Fur). Despite having been studied extensively, the comprehensive physiological roles and mechanisms of Fur-coordinated iron metabolism still remain obscure. In this work, by integrating a high-resolution transcriptomic study of the Fur wild-type and knockout K-12 strains in the presence or absence of iron with high-throughput ChIP-seq assay and physiological studies, we revisited the regulatory roles of iron and Fur systematically and discovered several intriguing features of Fur regulation. The size of the Fur regulon was expanded greatly, and significant discrepancies were observed to exist between the regulations of Fur on the genes under its direct repression and activation. Fur showed stronger binding strength to the genes under its repression, and genes that were repressed by Fur were more sensitive to Fur and iron regulation as compared to the genes that were activated by Fur. Finally, we found that Fur linked iron metabolism to many essential processes, and the systemic regulations of Fur on carbon metabolism, respiration, and motility were further validated or discussed. These results highlight how Fur and Fur-controlled iron metabolism affect many cellular processes in a systematic way.