Evolutionary Optimization of Transcription Factor Binding Motif Detection

2014 ◽  
pp. 261-274 ◽  
Author(s):  
Zhao Zhang ◽  
Ze Wang ◽  
Guoqin Mai ◽  
Youxi Luo ◽  
Miaomiao Zhao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factor Binding ◽  
Evolutionary Optimization ◽  
Binding Motif ◽  
Transcription Factor Binding Motif ◽  
Factor Binding ◽  
Motif Detection

scholarly journals Rational gRNA Design Based on Transcription Factor Binding Data

2021 ◽  
Author(s):  
David Bergenholm ◽  
Yasaman Dabirian ◽  
Raphael Ferreira ◽  
Verena Siewers ◽  
Florian David ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genome Engineering ◽  
Transcription Factor Binding ◽  
Central Carbon Metabolism ◽  
Binding Motif ◽  
Transcription Factor Binding Motif ◽  
Factor Binding ◽  
Transcription Factor Motif ◽  
Binding Data ◽  
Genes Encoding

Abstract The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has become a standard tool in many genome engineering endeavors. The endonuclease-deficient version of Cas9 (dCas9) is also a powerful programmable tool for gene regulation. In this study, we made use of Saccharomyces cerevisiae transcription factor binding data to obtain a better understanding of the interplay between transcription factor binding and binding of dCas9 fused to an activator domain, VPR. More specifically, we targeted dCas9-VPR towards binding sites of Gcr1-Gcr2 and Tye7 present in several promoters of genes encoding enzymes engaged in the central carbon metabolism. From our data, we observed an upregulation of gene expression when dCas9-VPR was targeted next to a transcription factor binding motif, whereas downregulation or no change was observed when dCas9 was bound on a transcription factor motif. This suggests a steric competition between dCas9 and the specific transcription factor. Integrating transcription factor binding data, therefore, proved to be useful for designing gRNAs for CRISPRi/a applications.

scholarly journals RSAT matrix-clustering: dynamic exploration and redundancy reduction of transcription factor binding motif collections

2017 ◽  
Vol 45 (13) ◽  
pp. e119-e119 ◽  
Author(s):  
Jaime Abraham Castro-Mondragon ◽  
Sébastien Jaeger ◽  
Denis Thieffry ◽  
Morgane Thomas-Chollier ◽  
Jacques van Helden
Keyword(s):  
Transcription Factor ◽  
Transcription Factor Binding ◽  
Binding Motif ◽  
Transcription Factor Binding Motif ◽  
Factor Binding ◽  
Redundancy Reduction

scholarly journals Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Giovanna Ambrosini ◽  
Ilya Vorontsov ◽  
Dmitry Penzar ◽  
Romain Groux ◽  
Oriol Fornes ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factor Binding ◽  
Binding Motif ◽  
Transcription Factor Binding Motif ◽  
Factor Binding

scholarly journals Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development

2017 ◽  
Vol 114 (23) ◽  
pp. 5854-5861 ◽  
Author(s):  
Gregory A. Cary ◽  
Alys M. Cheatle Jarvela ◽  
Rene D. Francolini ◽  
Veronica F. Hinman
Keyword(s):  
Transcription Factor ◽  
Sea Urchins ◽  
Transcription Factor Binding ◽  
Model Systems ◽  
Binding Motif ◽  
Regulatory Sequences ◽  
Binding Motifs ◽  
Chip Sequencing ◽  
Factor Binding ◽  
Genome Wide

Sea stars and sea urchins are model systems for interrogating the types of deep evolutionary changes that have restructured developmental gene regulatory networks (GRNs). Although cis-regulatory DNA evolution is likely the predominant mechanism of change, it was recently shown that Tbrain, a Tbox transcription factor protein, has evolved a changed preference for a low-affinity, secondary binding motif. The primary, high-affinity motif is conserved. To date, however, no genome-wide comparisons have been performed to provide an unbiased assessment of the evolution of GRNs between these taxa, and no study has attempted to determine the interplay between transcription factor binding motif evolution and GRN topology. The study here measures genome-wide binding of Tbrain orthologs by using ChIP-sequencing and associates these orthologs with putative target genes to assess global function. Targets of both factors are enriched for other regulatory genes, although nonoverlapping sets of functional enrichments in the two datasets suggest a much diverged function. The number of low-affinity binding motifs is significantly depressed in sea urchins compared with sea star, but both motif types are associated with genes from a range of functional categories. Only a small fraction (∼10%) of genes are predicted to be orthologous targets. Collectively, these data indicate that Tbr has evolved significantly different developmental roles in these echinoderms and that the targets and the binding motifs in associated cis-regulatory sequences are dispersed throughout the hierarchy of the GRN, rather than being biased toward terminal process or discrete functional blocks, which suggests extensive evolutionary tinkering.

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