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- Title
Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors.
- Authors
Berenson, Anna; Lane, Ryan; Soto-Ugaldi, Luis F.; Patel, Mahir; Ciausu, Cosmin; Li, Zhaorong; Chen, Yilin; Shah, Sakshi; Santoso, Clarissa; Liu, Xing; Spirohn, Kerstin; Hao, Tong; Hill, David E.; Vidal, Marc; Fuxman Bass, Juan I.
- 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. Combinations of transcription factors (TFs) bind DNA to fine-tune gene expression. Here, the authors map cooperative and antagonistic DNA binding across hundreds of TF-pairs. TF-TF relationships vary depending on DNA targets and TF isoforms.
- Subjects
TRANSCRIPTION factors; HUMAN papillomavirus; VIRAL proteins; GENE expression; YEAST
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-42445-6