Co-SELECT reveals sequence non-specific contribution of DNA shape to transcription factor binding in vitro.
Nucleic Acids Res
; 47(13): 6632-6641, 2019 07 26.
Article
en En
| MEDLINE
| ID: mdl-31226207
ABSTRACT
Understanding the principles of DNA binding by transcription factors (TFs) is of primary importance for studying gene regulation. Recently, several lines of evidence suggested that both DNA sequence and shape contribute to TF binding. However, the following compelling question is yet to be considered in the absence of any sequence similarity to the binding motif, can DNA shape still increase binding probability? To address this challenge, we developed Co-SELECT, a computational approach to analyze the results of in vitro HT-SELEX experiments for TF-DNA binding. Specifically, Co-SELECT leverages the presence of motif-free sequences in late HT-SELEX rounds and their enrichment in weak binders allows Co-SELECT to detect an evidence for the role of DNA shape features in TF binding. Our approach revealed that, even in the absence of the sequence motif, TFs have propensity to bind to DNA molecules of the shape consistent with the motif specific binding. This provides the first direct evidence that shape features that accompany the preferred sequence motifs also bestow an advantage for weak, sequence non-specific binding.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Aptámeros de Nucleótidos
/
Técnica SELEX de Producción de Aptámeros
/
Conformación de Ácido Nucleico
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2019
Tipo del documento:
Article