Biology
Document Type
Article
Abstract
A long-standing objective in modern biology is to characterize the molecular components that drive the development of an organism. At the heart of eukaryotic development lies gene regulation. On the molecular level, much of the research in this field has focused on the binding of transcription factors (TFs) to regulatory regions in the genome known as cis-regulatory modules (CRMs). However, relatively little is known about the sequence-specific binding preferences of many TFs, especially with respect to the possible interdependencies between the nucleotides that make up binding sites. A particular limitation of many existing algorithms that aim to predict binding site sequences is that they do not allow for dependencies between nonadjacent nucleotides. In this study, we use a recently developed computational algorithm, MARZ, to compare binding site sequences using 32 distinct models in a system-atic and unbiased approach to explore nucleotide dependencies within binding sites for 15 distinct TFs known to be critical to Drosophila development. Our results indicate that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models that are used to predict binding sites. We also directly compare the ability of different models to identify the known KRUPPEL TF binding sites in CRMs and demonstrate that a more complex model that accounts for nucleotide interdependencies performs better when compared with simple models. This ability to identify TFs with critical nucleotide interdependencies in their binding sites will lead to a deeper understanding of how these molecular characteristics contribute to the architecture of CRMs and the precise regulation of transcription during organismal development.
Publication Title
Gene Regulation and Systems Biology
Publication Date
6-12-2016
Volume
10
First Page
21
Last Page
33
ISSN
1177-6250
DOI
10.4137/GRSB.S38462
Keywords
Binding site, Cis-regulatory module, Drosophila, Position weight matrix, Transcription factor
Repository Citation
Dresch, Jacqueline M.; Zellers, Rowan G.; Bork, Daniel K.; and Drewell, Robert A., "Nucleotide interdependency in transcription factor binding sites in the drosophila genome" (2016). Biology. 119.
https://commons.clarku.edu/faculty_biology/119
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Copyright Conditions
Dresch, J. M., Zellers, R. G., Bork, D. K., & Drewell, R. A. (2016). Nucleotide interdependency in transcription factor binding sites in the Drosophila genome. Gene regulation and systems biology, 10, GRSB-S38462.
