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

BMC Bioinformatics. 2014 Aug 26;15(1):288. doi: 10.1186/1471-2105-15-288.

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/ under the terms of the GNU General Public License.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA, A-Form / genetics*
  • DNA, A-Form / metabolism
  • GATA2 Transcription Factor / genetics
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Regulation
  • Genome / genetics*
  • Genomics / methods*
  • Nuclear Factor 90 Proteins / metabolism
  • Promoter Regions, Genetic / genetics*
  • Software*
  • Xenopus / genetics
  • Xenopus / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism

Substances

  • DNA, A-Form
  • GATA2 Transcription Factor
  • GATA2 protein, Xenopus
  • Nuclear Factor 90 Proteins
  • Xenopus Proteins