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Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors
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Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors
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Journal Article
Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors
2023
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Assaying
/ Binding
/ DNA
/ Epstein-Barr Virus Infections
/ Herpesvirus 4, Human - genetics
/ Herpesvirus 4, Human - metabolism
/ Humanities and Social Sciences
/ Humans
/ Isoforms
/ Proteins
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Science
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Yeast
