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

Anna Berenson, Ryan Lane, Luis F. Soto-Ugaldi, Mahir Patel, Cosmin Ciausu, Zhaorong Li, Yilin Chen, Sakshi Shah, Clarissa Santoso, Xing Liu, Kerstin Spirohn, Tong Hao, David E. Hill, Marc Vidal and Juan I. Fuxman Bass ()
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Anna Berenson: Boston University
Ryan Lane: Boston University
Luis F. Soto-Ugaldi: Tri-Institutional Program in Computational Biology and Medicine
Mahir Patel: Boston University
Cosmin Ciausu: Boston University
Zhaorong Li: Boston University
Yilin Chen: Boston University
Sakshi Shah: Boston University
Clarissa Santoso: Boston University
Xing Liu: Boston University
Kerstin Spirohn: Dana-Farber Cancer Institute
Tong Hao: Dana-Farber Cancer Institute
David E. Hill: Dana-Farber Cancer Institute
Marc Vidal: Dana-Farber Cancer Institute
Juan I. Fuxman Bass: Boston University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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 region-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 from human papillomaviruses, Epstein-Barr virus, and other viruses. Altogether, pY1H assays provide a broadly applicable framework to study how different functional relationships affect protein occupancy at regulatory DNA regions.

Date: 2023
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DOI: 10.1038/s41467-023-42445-6

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