Divergence in a Eukaryotic Transcription Factor's co-TF Dependence Involves Multiple Intrinsically Disordered Regions
Preprint
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 , 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.Keywords
All Related Versions
- Published version: Nature Communications, 16 (1), 1.
Funding Information
- National Institute of General Medical Sciences (R35GM137831)
- National Institute of General Medical Sciences (R01GM135658)
- National Institute of General Medical Sciences (T32GM008629)
- National Institute of General Medical Sciences (T32GM1454441)
This publication has 74 references indexed in Scilit:
- Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regionsMolecular Cell, 2023
- The strengths and limitations of using biolayer interferometry to monitor equilibrium titrations of biomoleculesProtein Science, 2020
- Evolutionary conservation of a core fungal phosphate homeostasis pathway coupled to development in Blastocladiella emersoniiFungal Genetics and Biology, 2018
- Disease Model of GATA4 Mutation Reveals Transcription Factor Cooperativity in Human CardiogenesisCell, 2016
- Genomic Regions Flanking E-Box Binding Sites Influence DNA Binding Specificity of bHLH Transcription Factors through DNA ShapeCell Reports, 2013
- Integrated Approaches Reveal Determinants of Genome-wide Binding and Function of the Transcription Factor Pho4Molecular Cell, 2011
- Chromatin decouples promoter threshold from dynamic rangeNature, 2008
- Interaction ofSaccharomyces cerevisiae Pho2 with Pho4 increases the accessibility of the activation domain of Pho4Molecular Genetics and Genomics, 1996
- The transcription factor, the Cdk, its cyclin and their regulator: directing the transcriptional response to a nutritional signal.The EMBO Journal, 1994
- The activation domain of a basic helix‐loop‐helix protein is masked by repressor interaction with domains distinct from that required for transcription regulation.The EMBO Journal, 1994