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.

Highlights

  • DNA shape analysis has been established in recent years as an approach that reveals determinants of protein-DNA binding specificity beyond the primary nucleotide sequence [1,2,3,4]

  • We demonstrate the value of analyzing DNA shape annotations using Genome Browser for DNA shape annotations (GBshape) by comparing the structural features of in vivo nucleosome binding sites from worm, fly and human [20] and the evolutionary conservation of DNA shape at transcription start sites (TSSs) across multiple Drosophila species [21]

  • We have developed a database of DNA shape annotations for whole genomes of 94 organisms

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Summary

Introduction

DNA shape analysis has been established in recent years as an approach that reveals determinants of protein-DNA binding specificity beyond the primary nucleotide sequence [1,2,3,4]. For each organism the database provides four genome browser tracks with annotations for Minor Groove Width (MGW), Propeller Twist (ProT), Roll and Helix Twist (HelT) [14]. We demonstrate the value of analyzing DNA shape annotations using GBshape by comparing the structural features of in vivo nucleosome binding sites from worm, fly and human [20] and the evolutionary conservation of DNA shape at transcription start sites (TSSs) across multiple Drosophila species [21].

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