Abstract
Transcription is an intricate mechanism and is orchestrated at the promoter region. The cognate motifs in the promoters are observed in only a subset of total genes across different domains of life. Hence, sequence-motif based promoter prediction may not be a holistic approach for whole genomes. Conversely, the DNA structural property, duplex stability is a characteristic of promoters and can be used to delineate them from other genomic sequences. In this study, we have used a DNA duplex stability based algorithm ‘PromPredict’ for promoter prediction in a broad range of eukaryotes, representing various species of yeast, worm, fly, fish, and mammal. Efficiency of the software has been tested in promoter regions of 48 eukaryotic systems. PromPredict achieves recall values, which range from 68 to 92% in various eukaryotes. PromPredict performs well in mammals, although their core promoter regions are GC rich. ‘PromPredict’ has also been tested for its ability to predict promoter regions for various transcript classes (coding and non-coding), TATA-containing and TATA-less promoters as well as on promoter sequences belonging to different gene expression variability categories. The results support the idea that differential DNA duplex stability is a potential predictor of promoter regions in various genomes.
Highlights
Genetic transcription program is initiated in a segment of DNA referred to as ‘promoter’ which serves as a platform for the assembly of pre-initiation complex to specify the transcription start sites (TSSs)[1]
Promoter regions (−500 to +100 relative to TSS) in S. cerevisiae, C. elegans and D. melanogaster show low stability compared to their downstream regions, with narrow less stable regions being observed at −19, −11 and −114 for S. cerevisiae, C. elegans, and D. melanogaster respectively
Promoter prediction using in-house software PromPredict in the promoter sequences of six eukaryotic systems S. cerevisiae, C. elegans, D. melanogaster, zebrafish, mouse and human with transcription start site (TSS) data along with 48 eukaryotic systems with translation start site (TLS) data reveals that differential stability is a good criterion for promoter prediction
Summary
Genetic transcription program is initiated in a segment of DNA referred to as ‘promoter’ which serves as a platform for the assembly of pre-initiation complex to specify the transcription start sites (TSSs)[1]. Experimental methods for locating promoter elements include techniques such as 5′-tag-based methods which characterize promoters and transcription initiation events, small RNA sequencing, as well as methods which capture DNA-bound proteins, including RNAPII, transcription factors and histone modifications[9] They provide a snapshot of all transcribed regions or DNA-protein interactions in the genome for specific experimental conditions[7,10]. DNA structural features such as flexibility/bendability, curvature, base stacking and duplex stability have been applied to characterize promoter regions[15,16,17,18,19] They are better predictors, as the structural features are comparatively conserved, more informative and widely applicable across genomes. An analysis of predictions for various gene expression variability classes and TATA-containing and TATA-less promoters in S. cerevisiae
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