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Nucleotide composition-linked divergence of vertebrate core promoter architecture.

ABSTRACT: Transcription initiation involves the recruitment of basal transcription factors to the core promoter. A variety of core promoter elements exists; however for most of these motifs, the distribution across species is unknown. Here we report on the comparison of human and amphibian promoter sequences. We have used oligo-capping in combination with deep sequencing to determine transcription start sites in Xenopus tropicalis. To systematically predict regulatory elements, we have developed a de novo motif finding pipeline using an ensemble of computational tools. A comprehensive comparison of human and amphibian promoter sequences revealed both similarities and differences in core promoter architecture. Some of the differences stem from a highly divergent nucleotide composition of Xenopus and human promoters. Whereas the distribution of some core promoter motifs is conserved independently of species-specific nucleotide bias, the frequency of another class of motifs correlates with the single nucleotide frequencies. This class includes the well-known TATA box and SP1 motifs, which are more abundant in Xenopus and human promoters, respectively. While these motifs are enriched above the local nucleotide background in both organisms, their frequency varies in step with this background. These differences are likely adaptive as these motifs can recruit TFIID to either CpG island or sharply initiating promoters. Our results highlight both the conserved and diverged aspects of vertebrate transcription, most notably showing co-opted motif usage to recruit the transcriptional machinery to promoters with diverging nucleotide composition. This shows how sweeping changes in nucleotide composition are compatible with highly conserved mechanisms of transcription initiation.

SUBMITTER: van Heeringen SJ

PROVIDER: S-EPMC3044855 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Nucleotide composition-linked divergence of vertebrate core promoter architecture.

van Heeringen Simon J SJ Akhtar Waseem W Jacobi Ulrike G UG Akkers Robert C RC Suzuki Yutaka Y Veenstra Gert Jan C GJ

Genome research 20110110 3

Transcription initiation involves the recruitment of basal transcription factors to the core promoter. A variety of core promoter elements exists; however for most of these motifs, the distribution across species is unknown. Here we report on the comparison of human and amphibian promoter sequences. We have used oligo-capping in combination with deep sequencing to determine transcription start sites in Xenopus tropicalis. To systematically predict regulatory elements, we have developed a de novo ...[more]

PMID: 21284373

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Project description:Transcription initiation regulation is mediated by sequence-specific interactions between DNA-binding proteins (transcription factors) and cis-elements, where BRE, TATA, INR, DPE and MTE motifs constitute canonical core motifs for basal transcription initiation of genes. Accurate identification of transcription start site (TSS) and their corresponding promoter regions is critical for delineation of these motifs. To this end, the genome scale analysis of core promoter architecture in insects has been confined to Drosophila. The recently sequenced Tsetse fly genome provides a unique opportunity to analyze transcription initiation regulation machinery in blood-feeding insects.A computational method for identification of TSS in newly sequenced Tsetse fly genome was evaluated, using TSS seq tags sampled from two developmental stages namely; larvae and pupae. There were 3134 tag clusters among which 45.4% (1424) of the tag clusters mapped to first coding exons or their proximal predicted 5'UTR regions and 1.0% (31) tag clusters mapping to transposons, within a threshold of 100 tags per cluster. These 1393 non transposon-derived core promoters had propensity for AT nucleotides. The -1/+1 and 1/+1 positions in D. melanogaster, and G. m. morsitans had propensity for CA and AA dinucleotides respectively. The 1393 tag clusters comprised narrow promoters (5%), broad with peak promoters (23%) and broad without peak promoters (72%). Two-way motif co-occurrence analysis showed that the MTE-DPE pair is over-represented in broad core promoters. The frequently occurring triplet motifs in all promoter classes are the INR-MTE-DPE, TATA-MTE-DPE and TATA-INR-DPE. Promoters without the TATA motif had higher frequency of the MTE and INR motifs than those observed in Drosophila, where the DPE motif occur more frequently in promoters without TATA motif. Gene ontology terms associated with developmental processes were overrepresented in the narrow and broad with peak promoters.The study has identified different motif combinations associated with broad promoters in a blood-feeding insect. In the case of TATA-less core promoters, G.m. morsitans uses the MTE to compensate for the lack of a TATA motif. The increasing availability of TSS seq data allows for revision of existing gene annotation datasets with the potential of identifying new transcriptional units.

Dataset Information

Nucleotide composition-linked divergence of vertebrate core promoter architecture.

Publications

Nucleotide composition-linked divergence of vertebrate core promoter architecture.

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