ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
The iron-sulfur accelerator YgfZ modulates genome-wide IHF-binding dynamics to regulate replication initiation in Escherichia coli
Kazutoshi Kasho
Rion Satomura
Mizuki Yoshida
Ryuki Murofushi
Ikuha Kitamura
Sho Nakagawa
Wataru Nakagaki
Tsutomu Katayama
Kyushu University, Fukuoka, Japan
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Abstract
In Escherichia coli, chromosome replication is regulated through ATP/ADP state of the DnaA initiator. The DDAH system inactivates DnaA in the post-initiation stage by promoting ATP hydrolysis through timely binding of the DNA-bending protein IHF to the datA locus, while the DARS2 locus reactivates DnaA in the pre-initiation stage via binding of IHF and another nucleoid protein Fis. The iron-sulfur cluster ([Fe-S]) assembly factor YgfZ is known to sustain replication initiation, central carbon metabolism, redox state and modification of tRNA A37 residues by MiaB, but the link between initiation and the others remains unclear. This study shows that YgfZ regulates initiation primarily by downregulating the DDAH system by repressing datA-IHF binding in a manner independent of MiaB. Also, the [Fe-S]-binding protein MnmA moderately downregulates datA-IHF binding. Furthermore, YgfZ globally downregulates basal IHF binding across the genome, while preserving IHF's timely binding at key loci including oriC and datA during the cell cycle, highlighting a novel strategy: YgfZ modulates both the cellular metabolic states and global genome dynamics to control replication initiation under various growth conditions.
Summary
Keywords
Data, DNAA, Escherichia coli, IHF, iron-sulfur cluster, Replication initiation, YgfZ
Received
05 January 2026
Accepted
18 February 2026
Copyright
© 2026 Kasho, Satomura, Yoshida, Murofushi, Kitamura, Nakagawa, Nakagaki and Katayama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Kazutoshi Kasho
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