Biology subjects

Ciausu, C.

Publications and source records attributed to Ciausu, C..

2 recordsLinked to original sources

bioRxiv2026

Multilayered specificity of transcription factor binding at cytokine promoters

Transcription factors (TFs) regulate gene expression through sequence-specific DNA binding, and their genomic occupancy is further influenced by TF expression, activation state, and protein-protein interactions. How these mechanisms determine context-specific gene regulation remains incompletely understood, particularly for tightly controlled immune genes such as cytokines. Here, we use paired yeast one-hybrid (pY1H) assays to systematically examine DNA binding of 236 TFs and 392 TF-pairs across 106 cytokine gene promoters. Of the 1,619 TF-promoter interactions identified, 555 required TF cooperativity and 410 were antagonized by at least one TF partner, suggesting that TF-DNA binding is highly dependent on TF partners. Usage of different partners can drastically alter a TFs target repertoire and may result in the recruitment of different transcriptional cofactors. Integration with existing data on TF expression and activation further showed that cooperativity and antagonism provide additional, underappreciated layers of DNA-binding specificity.

systems biology↗

bioRxiv2023

Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors

Cooperativity and antagonism between transcription factors (TFs) can drastically modify their binding to regulatory DNA elements. While mapping these relationships between TFs is important for understanding their context-specific functions, existing approaches either rely on DNA binding motif predictions, interrogate one TF at a time, or study individual TFs in parallel. Here, we introduce paired yeast one-hybrid (pY1H) assays to detect cooperativity and antagonism across hundreds of TF-pairs at DNA regions of interest. We provide evidence that a wide variety of TFs are subject to modulation by other TFs in a DNA sequence-specific manner. We also demonstrate that TF-TF relationships are often affected by alternative isoform usage, and identify cooperativity and antagonism between human TFs and viral proteins. pY1H assays provide a broadly applicable framework to study how different functional relationships affect protein occupancy at regulatory DNA regions.

systems biology↗