APTE: identification of indirect read-out A-DNA promoter elements in genomes
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
BMC Bioinformatics 2014, 15:288 doi:10.1186/1471-2105-15-288Published: 26 August 2014
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.
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.
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.