Journal article
Divergence in a eukaryotic transcription factor’s co-TF dependence involves multiple intrinsically disordered regions
Nature communications, Vol.16(1), 5340
06/18/2025
DOI: 10.1038/s41467-025-59244-w
PMCID: PMC12177071
PMID: 40533454
Abstract
Combinatorial control by transcription factors (TFs) is central to eukaryotic gene regulation, yet its mechanism, evolution, and regulatory impact are not well understood. Here we use natural variation in the yeast phosphate starvation (PHO) response to examine the genetic basis and species variation in TF interdependence. In
Saccharomyces cerevisiae
, the main TF Pho4 relies on the co-TF Pho2 to regulate ~28 genes, whereas in the related pathogen
Candida glabrata
, Pho4 has reduced Pho2 dependence and regulates ~70 genes. We found
C. glabrata
Pho4 (CgPho4) binds the same motif with 3–4 fold higher affinity. Machine learning and yeast one-hybrid assay identify two intrinsically disordered regions (IDRs) in CgPho4 that boost its activation domain’s activity. In ScPho4, an IDR next to the DNA binding domain both allows for enhanced activity with Pho2 and inhibits activity without Pho2. This study reveals how IDR divergence drives TF interdependence evolution by influencing activation potential and autoinhibition.
Here, the authors identify mechanistic differences in the dependence on co-transcription factors between orthologous TFs from two related yeast species, S. cerevisiae and C. glabrata. The investigation into intrinsically disordered regions sheds light on the role of autoinhibition in the reliance on co-TFs.
Details
- Title: Subtitle
- Divergence in a eukaryotic transcription factor’s co-TF dependence involves multiple intrinsically disordered regions
- Creators
- Lindsey F. Snyder - University of IowaEmily M. O’Brien - University of Iowa, BiologyJia ZhaoJinye Liang - University of IowaBaylee J. Bruce - University of IowaYuning Zhang - Duke UniversityWei Zhu - Duke UniversityThomas H. Cassier - University of IowaNicholas J. Schnicker - University of IowaXu Zhou - Boston Children's HospitalRaluca Gordân - Duke UniversityBin Z. He - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.16(1), 5340
- DOI
- 10.1038/s41467-025-59244-w
- PMID
- 40533454
- PMCID
- PMC12177071
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group UK
- Grant note
- R35GM137831; T32GM008629; T32GM1454441 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) (https://doi.org/10.13039/100000057)
- Language
- English
- Date published
- 06/18/2025
- Academic Unit
- Molecular Physiology and Biophysics; Biology; Medicine Administration
- Record Identifier
- 9984832183702771
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