Abstract
BackgroundGene expression in the Drosophila embryo is controlled by functional interactions between a large network of protein transcription factors (TFs) and specific sequences in DNA cis-regulatory modules (CRMs). The binding site sequences for any TF can be experimentally determined and represented in a position weight matrix (PWM). PWMs can then be used to predict the location of TF binding sites in other regions of the genome, although there are limitations to this approach as currently implemented.ResultsIn this proof-of-principle study, we analyze 127 CRMs and focus on four TFs that control transcription of target genes along the anterio-posterior axis of the embryo early in development. For all four of these TFs, there is some degree of conserved flanking sequence that extends beyond the predicted binding regions. A potential role for these conserved flanking sequences may be to enhance the specificity of TF binding, as the abundance of these sequences is greatly diminished when we examine only predicted high-affinity binding sites.ConclusionsExpanding PWMs to include sequence context-dependence will increase the information content in PWMs and facilitate a more efficient functional identification and dissection of CRMs.
Highlights
Gene expression in the Drosophila embryo is controlled by functional interactions between a large network of protein transcription factors (TFs) and specific sequences in DNA cis-regulatory modules (CRMs)
Our analysis indicates that the current position weight matrix (PWM) for all four TFs examined exclude significant biases towards a given base, or bases, in specific positions in the neighboring sequences and that the information content of these PWMs can be improved by including these additional sequences
CRMs that are active during early Drosophila development for predicted binding regions for four TFs using
Summary
Gene expression in the Drosophila embryo is controlled by functional interactions between a large network of protein transcription factors (TFs) and specific sequences in DNA cis-regulatory modules (CRMs). The binding site sequences for any TF can be experimentally determined and represented in a position weight matrix (PWM). The control of gene expression during development in Drosophila and other metazoans is tightly directed by cisacting regulatory sequences in the genome. These DNA sequences modulate expression of target genes by binding protein transcription factors (TFs) [1]. Once a PWM is constructed, these models aid in the discovery of de novo binding sites in silico, providing predictions for the location of additional binding regions in the genome, without the need for technically challenging in vitro binding assays [10,14]
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