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Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.

ABSTRACT: The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modeling scheme based on the assumption that chromosome architecture is maintained by protein bridges, which form chromatin loops. To test the model, we perform FISH experiments and compare with Capture-C data. Starting merely from the locations of protein binding sites, our model accurately predicts the experimentally observed chromatin interactions, revealing a population of 3D conformations.

SUBMITTER: Brackley CA

PROVIDER: S-EPMC4815170 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.

Brackley Chris A CA Brown Jill M JM Waithe Dominic D Babbs Christian C Davies James J Hughes Jim R JR Buckle Veronica J VJ Marenduzzo Davide D

Genome biology 20160331

The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modeling scheme based on the assumption that chromosome architecture is maintained by protein bridges, which form chromatin loops. To test the model, we perform FISH experiments and compare with ...[more]

PMID: 27036497

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Project description:While hundreds of microbial genomes are sequenced, the challenge remains to define their cis-regulatory maps. Here, we present a comparative genomic analysis of the cis-regulatory map of Shewanella oneidensis, an important model organism for bioremediation because of its extraordinary abilities to use a wide variety of metals and organic molecules as electron acceptors in respiration. First, from the experimentally verified transcriptional regulatory networks of Escherichia coli, we inferred 24 DNA motifs that are conserved in S. oneidensis. We then applied a new comparative approach on five Shewanella genomes that allowed us to systematically identify 194 nonredundant palindromic DNA motifs and corresponding regulons in S. oneidensis. Sixty-four percent of the predicted motifs are conserved in at least three of the seven newly sequenced and distantly related Shewanella genomes. In total, we obtained 209 unique DNA motifs in S. oneidensis that cover 849 unique transcription units. Besides conservation in other genomes, 77 of these motifs are supported by at least one additional type of evidence, including matching to known transcription factor binding motifs and significant functional enrichment or expression coherence of the corresponding target genes. Using the same approach on a more focused gene set, 990 differentially expressed genes derived from published microarray data of S. oneidensis during exposure to metal ions, we identified 31 putative cis-regulatory motifs (16 with at least one type of additional supporting evidence) that are potentially involved in the process of metal reduction. The majority (18/31) of those motifs had been found in our whole-genome comparative approach, further demonstrating that such an approach is capable of uncovering a large fraction of the regulatory map of a genome even in the absence of experimental data. The integrated computational approach developed in this study provides a useful strategy to identify genome-wide cis-regulatory maps and a novel avenue to explore the regulatory pathways for particular biological processes in bacterial systems.

Dataset Information

Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.

Publications

Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.

Similar Datasets

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