Cross-regulation of iron and phosphate homeostasis by Fep1 and Pho7 in fission yeast
- 1Department of Systems Biotechnology, Chung-Ang University, Anseong, Republic of Korea
- 2Department of Molecular Bioscience, Kangwon National University, Chuncheon, Republic of Korea
Abstract
Iron and phosphate are essential micronutrients with partially interconnected homeostatic control; however, the underlying transcriptional mechanisms that integrate these signals in the fission yeast Schizosaccharomyces pombe remain unclear. Fep1 (GATA-type repressor) is a key regulator of iron-uptake genes, whereas Pho7 (Zn2Cys6-family transcription factor) drives phosphate starvation response. However, whether each of the two factors influences the target regulon controlled by the other remains unclear. We combined genome-wide chromatin immunoprecipitation sequencing, RNA sequencing, and auxin-inducible degron-mediated acute depletion to define the joint Fep1–Pho7 transcriptional control and regulatory landscapes under defined iron and phosphate conditions. Unexpectedly, these analyses showed extensive overlap in chromatin occupancy between Fep1 and Pho7 at a subset of target promoters. Fep1 bound not only to canonical iron-uptake genes but also to the pho7+ locus and multiple phosphate-responsive promoters, whereas Pho7 showed association with a defined subset of Fep1 targets. Acute depletion experiments showed that Fep1 loss substantially increased Pho7 chromatin occupancy at iron-responsive promoters. Under iron-depleted conditions, Pho7 contributed to the transcriptional activation of specific Fep1 target genes (fio1+/fip1+ and str3+), which indicated that Pho7 supports iron uptake gene expression when Fep1 repression is attenuated. Condition-dependent binding analyses showed that iron availability influences the relative regulatory contribution of the two factors at shared loci. These findings support a model in which Fep1 and Pho7 form a cross-regulatory module that converges on shared genes to enable iron-dependent redistribution of their influence. Together, these findings suggest a mechanistic framework for integrating iron and phosphate signals at the promoter level in fission yeast.
IMPORTANCE: Iron and phosphate are essential micronutrients requiring balanced cellular levels for metabolism, redox control, and stress resistance. However, the transcriptional logic that integrates these signals remains unclear. Although fission yeast provides a powerful model for nutrient signaling, the iron-responsive factor Fep1 and the phosphate-responsive factor Pho7 have been treated as independent regulators. This study shows that Fep1 and Pho7 occupy promoters regulated by each other, supporting iron-dependent transcriptional cross-regulation. These findings suggest functional interplay between canonical iron- and phosphate-responsive pathways, although indirect metabolic coupling cannot be excluded. The iron-dependent shift in regulatory hierarchy between Fep1 and Pho7 at co-occupied promoters provides a mechanistic framework for understanding how cells can prioritize and integrate competing micronutrient demands. Therefore, cross-regulatory interactions between nutrient-specific transcription factors could indicate a general strategy for organizing multi-element homeostasis in fungi and may explain adaptation of pathogenic or commensal yeasts to fluctuating metal and phosphate environmental conditions.
Related
- Canavanine-based assay for gross chromosomal rearrangements reveals genome instability hotspots and modulating genes in fission yeast
- Ectopic overproduction of cell wall glucan through membrane perturbation by an antifungal peptide theonellamide A in fission yeast
- ROS Is Necessary for Dormancy Breaking in Fission Yeast Spores, While Its Downregulation by Sod1 Is Crucial for Later Events.
- Terminal hydroxylation of eIF5A hypusination influences mitochondrial protein expression and cellular metabolism in fission yeast
- Distinct ways by which Srs2 helicase and Rrp1 translocase shape Rad51–DNA interactions in fission yeast
BibTeX
@article{park2026crossregulation,
title = {{Cross-regulation of iron and phosphate homeostasis by Fep1 and Pho7 in fission yeast}},
author = {Seon-Ju Park and Yong-Joon Cho and Kyoung-Dong Kim},
journal = {Microbiology Spectrum},
year = {2026},
month = oct,
doi = {10.1128/spectrum.00716-26},
url = {https://doi.org/10.1128/spectrum.00716-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cross-regulation of iron and phosphate homeostasis by Fep1 and Pho7 in fission yeast
AU - Seon-Ju Park
AU - Yong-Joon Cho
AU - Kyoung-Dong Kim
PY - 2026
DA - 2026/10/02
JO - Microbiology Spectrum
DO - 10.1128/spectrum.00716-26
UR - https://doi.org/10.1128/spectrum.00716-26
AB - Iron and phosphate are essential micronutrients with partially interconnected homeostatic control; however, the underlying transcriptional mechanisms that integrate these signals in the fission yeast Schizosaccharomyces pombe remain unclear. Fep1 (GATA-type repressor) is a key regulator of iron-uptake genes, whereas Pho7 (Zn2Cys6-family transcription factor) drives phosphate starvation response. However, whether each of the two factors influences the target regulon controlled by the other remains unclear. We combined genome-wide chromatin immunoprecipitation sequencing, RNA sequencing, and auxin-inducible degron-mediated acute depletion to define the joint Fep1–Pho7 transcriptional control and regulatory landscapes under defined iron and phosphate conditions. Unexpectedly, these analyses showed extensive overlap in chromatin occupancy between Fep1 and Pho7 at a subset of target promoters. Fep1 bound not only to canonical iron-uptake genes but also to the pho7+ locus and multiple phosphate-responsive promoters, whereas Pho7 showed association with a defined subset of Fep1 targets. Acute depletion experiments showed that Fep1 loss substantially increased Pho7 chromatin occupancy at iron-responsive promoters. Under iron-depleted conditions, Pho7 contributed to the transcriptional activation of specific Fep1 target genes (fio1+/fip1+ and str3+), which indicated that Pho7 supports iron uptake gene expression when Fep1 repression is attenuated. Condition-dependent binding analyses showed that iron availability influences the relative regulatory contribution of the two factors at shared loci. These findings support a model in which Fep1 and Pho7 form a cross-regulatory module that converges on shared genes to enable iron-dependent redistribution of their influence. Together, these findings suggest a mechanistic framework for integrating iron and phosphate signals at the promoter level in fission yeast. IMPORTANCE: Iron and phosphate are essential micronutrients requiring balanced cellular levels for metabolism, redox control, and stress resistance. However, the transcriptional logic that integrates these signals remains unclear. Although fission yeast provides a powerful model for nutrient signaling, the iron-responsive factor Fep1 and the phosphate-responsive factor Pho7 have been treated as independent regulators. This study shows that Fep1 and Pho7 occupy promoters regulated by each other, supporting iron-dependent transcriptional cross-regulation. These findings suggest functional interplay between canonical iron- and phosphate-responsive pathways, although indirect metabolic coupling cannot be excluded. The iron-dependent shift in regulatory hierarchy between Fep1 and Pho7 at co-occupied promoters provides a mechanistic framework for understanding how cells can prioritize and integrate competing micronutrient demands. Therefore, cross-regulatory interactions between nutrient-specific transcription factors could indicate a general strategy for organizing multi-element homeostasis in fungi and may explain adaptation of pathogenic or commensal yeasts to fluctuating metal and phosphate environmental conditions.
SN - 2165-0497
ER -