Dataset Information

An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance.

ABSTRACT:

Background

Motif finding algorithms have developed in their ability to use computationally efficient methods to detect patterns in biological sequences. However the posterior classification of the output still suffers from some limitations, which makes it difficult to assess the biological significance of the motifs found. Previous work has highlighted the existence of positional bias of motifs in the DNA sequences, which might indicate not only that the pattern is important, but also provide hints of the positions where these patterns occur preferentially.

Results

We propose to integrate position uniformity tests and over-representation tests to improve the accuracy of the classification of motifs. Using artificial data, we have compared three different statistical tests (Chi-Square, Kolmogorov-Smirnov and a Chi-Square bootstrap) to assess whether a given motif occurs uniformly in the promoter region of a gene. Using the test that performed better in this dataset, we proceeded to study the positional distribution of several well known cis-regulatory elements, in the promoter sequences of different organisms (S. cerevisiae, H. sapiens, D. melanogaster, E. coli and several Dicotyledons plants). The results show that position conservation is relevant for the transcriptional machinery.

Conclusion

We conclude that many biologically relevant motifs appear heterogeneously distributed in the promoter region of genes, and therefore, that non-uniformity is a good indicator of biological relevance and can be used to complement over-representation tests commonly used. In this article we present the results obtained for the S. cerevisiae data sets.

SUBMITTER: Casimiro AC

PROVIDER: S-EPMC2375121 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Publications

An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance.

Casimiro Ana C AC Vinga Susana S Freitas Ana T AT Oliveira Arlindo L AL

BMC bioinformatics 20080207

<h4>Background</h4>Motif finding algorithms have developed in their ability to use computationally efficient methods to detect patterns in biological sequences. However the posterior classification of the output still suffers from some limitations, which makes it difficult to assess the biological significance of the motifs found. Previous work has highlighted the existence of positional bias of motifs in the DNA sequences, which might indicate not only that the pattern is important, but also pr ...[more]

PMID: 18257925

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Project description:Extracytoplasmic function (ECF) ? factors are the largest and the most diverse group of alternative ? factors, but their mechanisms of transcription are poorly studied. This subfamily is considered to exhibit a rigid promoter structure and an absence of mixing and matching; both -35 and -10 elements are considered necessary for initiating transcription. This paradigm, however, is based on very limited data, which bias the analysis of diverse ECF ? subgroups. Here we investigate DNA and protein recognition motifs involved in ECF ? factor transcription by a computational analysis of canonical ECF subfamily members, much less studied ECF ? subgroups, and the group outliers, obtained from recently sequenced bacteriophages. The analysis identifies an extended -10 element in promoters for phage ECF ? factors; a comparison with bacterial ? factors points to a putative 6-amino-acid motif just C-terminal of domain ?2, which is responsible for the interaction with the identified extension of the -10 element. Interestingly, a similar protein motif is found C-terminal of domain ?2 in canonical ECF ? factors, at a position where it is expected to interact with a conserved motif further upstream of the -10 element. Moreover, the phiEco32 ECF ? factor lacks a recognizable -35 element and ?4 domain, which we identify in a homologous phage, 7-11, indicating that the extended -10 element can compensate for the lack of -35 element interactions. Overall, the results reveal greater flexibility in promoter recognition by ECF ? factors than previously recognized and raise the possibility that mixing and matching also apply to this group, a notion that remains to be biochemically tested.ECF ? factors are the most numerous group of alternative ? factors but have been little studied. Their promoter recognition mechanisms are obscured by the large diversity within the ECF ? factor group and the limited similarity with the well-studied housekeeping ? factors. Here we extensively compare bacterial and bacteriophage ECF ? factors and their promoters in order to infer DNA and protein recognition motifs involved in transcription initiation. We predict a more flexible promoter structure than is recognized by the current paradigm, which assumes rigidness, and propose that ECF ? promoter elements may complement (mix and match with) each other's strengths. These results warrant the refocusing of research efforts from the well-studied housekeeping ? factors toward the physiologically highly important, but insufficiently understood, alternative ? factors.

Dataset Information

An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance.

Background

Results

Conclusion

Publications

An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance.

Similar Datasets

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