التفاصيل البيبلوغرافية
| العنوان: |
Accurate and sensitive quantification of protein-DNA binding affinity |
| المؤلفون: |
Rastogi, Chaitanya, Rube, Hans Tomas, Kribelbauer, Judith Franziska, Crocker, Justin, Loker, Ryan Edmund, Martini, Gabriella D., Laptenko, Oleg, Freed-Pastor, William Allen, Prives, Carol L., Stern, David L., Mann, Richard S., Bussemaker, Harmen J. |
| سنة النشر: |
2018 |
| المجموعة: |
Columbia University: Academic Commons |
| مصطلحات موضوعية: |
Transcription factors, DNA-protein interactions, Protein binding, Probabilities--Mathematical models |
| الوصف: |
Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
https://doi.org/10.7916/D85H9079Test |
| DOI: |
10.7916/D85H9079 |
| الإتاحة: |
https://doi.org/10.7916/D85H9079Test |
| رقم الانضمام: |
edsbas.33D2898A |
| قاعدة البيانات: |
BASE |
