GBshape: a genome browser database for DNA shape annotations

Abstract

Many regulatory mechanisms require a high degree of specificity in protein-DNA binding. Nucleotide sequence does not provide an answer to the question of why a protein binds only to a small subset of the many putative binding sites in the genome that share the same core motif. Whereas higher-order effects, such as chromatin accessibility, cooperativity and cofactors, have been described, DNA shape recently gained attention as another feature that fine-tunes the DNA binding specificities of some transcription factor families. Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.

Figure 1.

Architecture of the GBshape database. GBshape consists of a high-throughput prediction platform, data depositories and a user interface. DNA shape annotations of entire genomes can be generated by the high-throughput prediction platform, which runs on a high-performance computing cluster (HPCC), and, together with genome sequences and UCSC Genome Browser standard annotations, stored in the data depositories. The user interface provides multiple functionalities for users to either visualize or download structural annotations.

Figure 2.

Visual display of GBshape annotations in the genome browser for a specific position in the S. cerevisiae genome. (A) Genome positions and UCSC Genome Browser standard annotation tracks. (B) DNA shape annotation tracks for MGW, ProT, Roll, HelT and hydroxyl radical cleavage intensity (ORChID2). (C) Heat map views for DNA shape annotations.

Figure 3.

Variation in MGW (blue) and ORChID2 (green) signals on average in nucleosome sequences from the (A) Caenorhabditis elegans, (B) Drosophila melanogaster and (C) human genomes. Numbering of the nucleotide position starts with −1 and 1 for the central two base pairs, respectively.

Figure 4.

Variation in Roll (blue), HelT (green) and ProT (red) on average in nucleosome sequences from the (A) Caenorhabditis elegans, (B) Drosophila melanogaster and (C) human genomes. Numbering of the nucleotide position starts with −1 and 1 for the central two base pairs, respectively.

Figure 5.

Average heat maps for four DNA shape features of TSSs and 50 bp up- and downstream in four fly species. The analysis is based on 3823 TSSs from the D. melanogaster, 6909 TSSs from the D. simulans, 7234 TSSs from the D. sechellia and 7397 TSSs from the D. pseudoobscura genomes. Column numbers in each heat map indicate the nucleotide position relative to the TSS. Black frames mark the locations of the Initiatior (Inr) element and TATA box.