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Series GSE223013 Query DataSets for GSE223013
Status Public on Jan 20, 2023
Title UV irradiation remodels the specificity landscape of transcription factors [84702_Proteins]
Platform organism synthetic construct
Sample organism Homo sapiens
Experiment type Other
Summary Somatic mutations are highly enriched at transcription factor (TF) binding sites, with the strongest trend being observed for ultraviolet light (UV)-induced mutations in melanomas. One of the main mechanisms proposed for this hyper-mutation pattern is the inefficient repair of UV lesions within TF-binding sites, caused by competition between TFs bound to these lesions and the DNA repair proteins that must recognize the lesions to initiate repair. However, TF binding to UV-irradiated DNA is poorly characterized, and it is unclear whether TFs maintain specificity for their DNA sites after UV exposure. We developed UV-Bind, a high-throughput approach to investigate the impact of UV irradiation on protein-DNA binding specificity. We applied UV-Bind to ten TFs from eight structural families, and found that UV lesions significantly altered the DNA-binding preferences of all TFs tested. The main effect was a decrease in binding specificity, but the precise effects and their magnitude differ across factors. Importantly, we found that despite the overall reduction in DNA-binding specificity in the presence of UV lesions, TFs can still compete with repair proteins for lesion recognition, in a manner consistent with their specificity for UV-irradiated DNA. In addition, for a subset of TFs we identified a surprising but reproducible effect at certain non-consensus DNA sequences, where UV irradiation leads to a high increase in the level of TF binding. These changes in DNA-binding specificity after UV irradiation, at both consensus and non-consensus sites, have important implications for the regulatory and mutagenic roles of TFs in the cell.
Overall design The UV-Bind assay was performed for 10 transcription factors and 1 repair protein (UV-DDB) for UV-irradiated arrays. This array uses a universal design that allows for the measurement of k-mers, and it was used to measure ETS1 and c-MYC binding. A detailed description is provided in the manuscript.
Contributor(s) Mielko Z, Gordan R
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Submission date Jan 17, 2023
Last update date Jan 23, 2023
Contact name Raluca Gordan
Organization name Duke University
Department Center for Genomic and Computational Biology
Street address 101 Science Dr, CIEMAS 2179
City Durham
State/province NC
ZIP/Postal code 27708
Country USA
Platforms (1)
GPL33026 Duke/084702
Samples (4)
GSM6938264 ETS1_NonUV
GSM6938265 ETS1_UV
GSM6938266 MYC_NonUV
This SubSeries is part of SuperSeries:
GSE223023 UV irradiation remodels the specificity landscape of transcription factors
BioProject PRJNA924719

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE223013_RAW.tar 25.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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