Analysis of the nucleotide content of Escherichia coli promoter sequences related to the alternative sigma factors

Abstract

Promoters are DNA sequences located upstream of the transcription start site of genes. In bacteria, the RNA polymerase enzyme requires additional subunits, called sigma factors (σ) to begin specific gene transcription in distinct environmental conditions. Currently, promoter prediction still poses many challenges due to the characteristics of these sequences. In this paper, the nucleotide content of Escherichia coli promoter sequences, related to five alternative σ factors, was analyzed by a machine learning technique in order to provide profiles according to the σ factor which recognizes them. For this, the clustering technique was applied since it is a viable method for finding hidden patterns on a data set. As a result, 20 groups of sequences were formed, and, aided by the Weblogo tool, it was possible to determine sequence profiles. These found patterns should be considered for implementing computational prediction tools. In addition, evidence was found of an overlap between the functions of the genes regulated by different σ factors, suggesting that DNA structural properties are also essential parameters for further studies.

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“…They are often perceived as short-sized and AT-rich sequences, presenting low degrees of conservation (i.e. the motifs located on the -10 and -35 regions often are not found to be in accordance with their canonical motif -both in structure and position) [3]. For instance, promoter sequences related to the σ 54 , instead of presenting its motifs located on the -10 and -35, are commonly found in the -12 and -24 regions.…”

“…Each σ factor interacts with specific DNA promoter sequences. As example, the housekeeping factor (σ 70 ) is known to regulate most of the genes involved in the vital processes of the bacteria, also maintaining the bulk of transcription during its growth phase [2,3]. It also serves as the model for the canonical promoter, composed by two main motifs: one located at a 10 bp distance from the TSS, and another located 35 bp distant.…”

“…Furthermore, the -10 region is composed by a canonical 5' -TATAAT -3' sequence, while the -35 region is composed by a 5' -TTGACA -3' [4]. Each σ factor has its own set of features that distinct themselves from each other, including structural variations in the motifs (e.g., expected sequence, and degree of conservation), sometimes in the expected position of the motifs (such as the σ 54 , with its motifs located around -12 and -24 bp distant from the TSS), among others [1,3,4].…”

“…Overall, these distinct features give specificity to the transcription process, and the existence of these multiple σ factors allows the bacteria to survive adverse situationsfrom pH fluctuations to the stress provoked by heat shocks [3]. Hence the importance of thoroughly studying them, allowing opportunities to expand our comprehension in topics such as: (i) the mechanisms of gene expression regulation; (ii) comprehension of the mechanisms involved in diseases; (iii) development of novel drugs in the combat of bacterial infections, to mention a few [4][5][6].…”

Toward Algorithms for Automation of Postgenomic Data Analyses:Bacillus subtilisPromoter Prediction with Artificial Neural Network

“…It is also known that identification consists of a primary step in understanding the mechanisms of gene regulation and expression (Dall'Alba et al, 2019). Besides that, it even advances an understanding of gene structure and provides relevant functional information.…”