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

Abstract

BackgroundTranscriptional 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.ResultsIn 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.ConclusionsA 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.

A newly identified Rab-GDI paralogue has a role in neural development in amphibia

“…We have previously shown that the Xenopus gata2 promoter is regulated, at least partially, by an A-form DNA structure (Llewellyn et al 2009;Scarlett et al 2004). A range of genes were identified in a screen to reveal other, similarly regulated targets and our data suggested that the promoter of one of these genes was probably, like gata2, a target for the Ilf3 transcription factor (Whitley et al 2014), here we have described the identification and characterisation of this gene.…”

“…We have previously described a novel promoter type dependent on an A-form DNA structure and identified 86 such potential examples in the Xenopus tropicalis genome (Whitley et al 2014). Aform DNA is a an 'overwound', non-canonical DNA helical structure favoured by dehydration.…”

General hospital psychiatry in India: History, scope, and future

“…[ 4 ] After a few years, in 1938, Dr. KK Masani started psychiatric services at JJ Hospital. [ 6 ] This was followed by a once-a-week psychiatry clinic in in the Outpatient Department (OPD) of Patna Medical College Hospital in 1939, under the guidance of Dr. Ghoshal,[ 7 ] and another service by Dr. N S Vahia at KEM Hospital[ 8 ] in the 1940s in Mumbai. Patna Medical College also has the honor of having Professor LP Varma as its first MD psychiatry student in 1941.…”

Accurate prediction of B-form/A-form DNA conformation propensity from primary sequence: A machine learning and free energy handshake

“…These A-form segments can then be specifically recognized by DNA binding proteins during the indirect readout mechanism. Such APSs allow binding of certain transcription factor (TF) binding proteins 21 and could play a role in protein-DNA binding mechanisms. Recently, Li et al.…”

“…Whitley and coworkers 21 used Basham's trinucleotide solvation free energy method of A/B DNA structure prediction 6 to find A-DNA promoters in the Xenopus tropicalis genome. Owing to the limited applicability of the aforementioned method, we believe that our proposed ML model can be implemented on other genomes to find unknown A-DNA promoter DNA steps a priori.…”