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Open Access Research article

APTE: identification of indirect read-out A-DNA promoter elements in genomes

David C Whitley2, Valeria Runfola1, Peter Cary1, Liliya Nazlamova1, Matt Guille1 and Garry Scarlett1*

Author Affiliations

1 Biophysics Laboratories, School of Biological Sciences, Institute of Biomedical and Biomolecular Science, University of Portsmouth, King Henry Building, King Henry I Street, Portsmouth PO1 2DY, UK

2 Centre for Molecular Design, School of Pharmacy and Biomedical Sciences, Institute of Biomedical and Biomolecular Science, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK

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BMC Bioinformatics 2014, 15:288  doi:10.1186/1471-2105-15-288

Published: 26 August 2014

Abstract

Background

Transcriptional regulation is normally based on the recognition by a transcription factor of a defined base sequence in a process of direct read-out. However, the nucleic acid secondary and tertiary structure can also act as a recognition site for the transcription factor in a process known as indirect read-out, although this is much less understood. We have previously identified such a transcriptional control mechanism in early Xenopus development where the interaction of the transcription factor ilf3 and the gata2 promoter requires the presence of both an unusual A-form DNA structure and a CCAAT sequence. Rapid identification of such promoters elsewhere in the Xenopus and other genomes would provide insight into a less studied area of gene regulation, although currently there are few tools to analyse genomes in such ways.

Results

In this paper we report the implementation of a novel bioinformatics approach that has identified 86 such putative promoters in the Xenopus genome. We have shown that five of these sites are A-form in solution, bind to transcription factors and fully validated one of these newly identified promoters as interacting with the ilf3 containing complex CBTF. This interaction regulates the transcription of a previously uncharacterised downstream gene that is active in early development.

Conclusions

A Perl program (APTE) has located a number of potential A-form DNA promotor elements in the Xenopus genome, five of these putative targets have been experimentally validated as A-form and as targets for specific DNA binding proteins; one has also been shown to interact with the A-form binding transcription factor ilf3. APTE is available from http://www.port.ac.uk/research/cmd/software/ webcite under the terms of the GNU General Public License.

Keywords:
A-form DNA; Transcription; Xenopus; Promoter analysis