Abstract
BackgroundCorrect temporal and spatial gene expression during metazoan development relies on combinatorial interactions between different transcription factors. As a consequence, cis-regulatory elements often colocalize in clusters termed cis-regulatory modules. These may have requirements on organizational features such as spacing, order and helical phasing (periodic spacing) between binding sites. Due to the turning of the DNA helix, a small modification of the distance between a pair of sites may sometimes drastically disrupt function, while insertion of a full helical turn of DNA (10–11 bp) between cis elements may cause functionality to be restored. Recently, de novo motif discovery methods which incorporate organizational properties such as colocalization and order preferences have been developed, but there are no tools which incorporate periodic spacing into the model.ResultsWe have developed a web based motif discovery tool, HeliCis, which features a flexible model which allows de novo detection of motifs with periodic spacing. Depending on the parameter settings it may also be used for discovering colocalized motifs without periodicity or motifs separated by a fixed gap of known or unknown length. We show on simulated data that it can efficiently capture the synergistic effects of colocalization and periodic spacing to improve detection of weak DNA motifs. It provides a simple to use web interface which interactively visualizes the current settings and thereby makes it easy to understand the parameters and the model structure.ConclusionHeliCis provides simple and efficient de novo discovery of colocalized DNA motif pairs, with or without periodic spacing. Our evaluations show that it can detect weak periodic patterns which are not easily discovered using a sequential approach, i.e. first finding the binding sites and second analyzing the properties of their pairwise distances.
Highlights
Correct temporal and spatial gene expression during metazoan development relies on combinatorial interactions between different transcription factors
The precise specificity required for correct temporal and spatial transcription during metazoan development relies on combinatorial interactions between binding sites in relatively dense clusters [1]
Algorithm overview We propose a de novo method for motif discovery, HeliCis, which can find motif pairs separated by a distance that varies in a periodical manner
Summary
Correct temporal and spatial gene expression during metazoan development relies on combinatorial interactions between different transcription factors. Cisregulatory elements often colocalize in clusters termed cis-regulatory modules These may have requirements on organizational features such as spacing, order and helical phasing (periodic spacing) between binding sites. The precise specificity required for correct temporal and spatial transcription during metazoan development relies on combinatorial interactions between binding sites in relatively dense clusters [1] These clusters, termed cis-regulatory modules (CRMs), typically contain sites (cisregulatory elements) for several different transcriptional activators and repressors. CRMs may be unstructured, serving as "billboards" that bring DNA binding proteins into proximity [2] In this case, the balance of activators and repressors, rather than the order or spacing between factors, is the most important property. But with requirements on organizational features such as spacing, order and helical phasing between binding sites
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
