Identification of transcription factor binding sites from ChIP-seq data at high resolution

Bardet, Anaïs F.; Steinmann, Jonas; Bafna, Sangeeta; Knoblich, Juergen A.; Zeitlinger, Julia; Stark, Alexander

doi:10.1093/bioinformatics/btt470

Cited by 64 publications

(62 citation statements)

References 44 publications

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“…Chromatin states were predicted across the genome using ChromHMM (Ernst and Kellis 2012). p300 peaks were detected using the peakzilla software (Bardet et al 2013). See Supplemental Methods for details.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary conservation of the eumetazoan gene regulatory landscape

et al. 2014

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Despite considerable differences in morphology and complexity of body plans among animals, a great part of the gene set is shared among Bilateria and their basally branching sister group, the Cnidaria. This suggests that the common ancestor of eumetazoans already had a highly complex gene repertoire. At present it is therefore unclear how morphological diversification is encoded in the genome. Here we address the possibility that differences in gene regulation could contribute to the large morphological divergence between cnidarians and bilaterians. To this end, we generated the first genome-wide map of gene regulatory elements in a nonbilaterian animal, the sea anemone Nematostella vectensis. Using chromatin immunoprecipitation followed by deep sequencing of five chromatin modifications and a transcriptional cofactor, we identified over 5000 enhancers in the Nematostella genome and could validate 75% of the tested enhancers in vivo. We found that in Nematostella, but not in yeast, enhancers are characterized by the same combination of histone modifications as in bilaterians, and these enhancers preferentially target developmental regulatory genes. Surprisingly, the distribution and abundance of gene regulatory elements relative to these genes are shared between Nematostella and bilaterian model organisms. Our results suggest that complex gene regulation originated at least 600 million yr ago, predating the common ancestor of eumetazoans.

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Section: Discussionmentioning

confidence: 99%

Evolutionary conservation of the eumetazoan gene regulatory landscape

et al. 2014

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“…For example, some ChIP-seq peak-callers do not account for strand-specific information, while others just compute strand cross-correlation to estimate the fragment length, afterwards shifting the reads with respect to the other strand (Bailey et al, 2013). Software tools like GeneTrack (Albert et al, 2008), GPS-GEM (Guo et al, 2012), peakzilla (Bardet et al, 2013) and MACS (Feng et al, 2012) have been used for peak-calling in ChIP-exo data-sets. However, GeneTrack was designed with ChIP-chip and ChIP-seq in mind, thus requiring manual matching of ChIP-exo peakpairs located nearby on opposed DNA strands (Rhee and Pugh, 2011).…”

Section: Introductionmentioning

confidence: 99%

CexoR: an R/Bioconductor package to uncover high-resolution protein-DNA interactions in ChIP-exo replicates

Madrigal

2015

EMBnet j.

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For its unprecedented level of spatial resolution, chromatin immunoprecipitation combined with � exonuclease digestion followed by high-throughput sequencing (ChIP-exo) has the potential to replace ChIP-seq as the standard approach for genome-wide mapping of protein-DNA interactions. In this assay, the midpoint between the strand-specific paired peaks, formed in the forward and reverse strands, is typically delimited by the exonuclease stop-sites, within which the protein-binding events are located. Although numerous algorithms have been developed for peak-calling in ChIP-seq data, none of them is fully adjusted for the analysis of ChIP-exo. This is because those statistical models do not make use of ChIP-exo's strand-specificity for the identification of protein-DNA binding sites. Here, we present the CexoR algorithm, which aims to ease the analysis of replicated ChIP-exo data in BAM alignment format. The detection algorithm relies on the Skellam distribution (cross-correlation of two Poisson distributions) to calculate probabilities of consecutive punctatesources of read-enrichment located nearby at Watson-and-Crick strands. ChIP-exo peak-pairs are identified and ranked by their irreproducible discovery rate estimated across biological replicates, and finally reported in BED format files. CexoR can potentially be applied to other ChIP-exo-based protocols, such as ChIP-nexus. Availability and implementation: CexoR has been implemented in R, and is freely available at http://bioconductor.org.

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“…Choice of peak calling algorithm and parameters were based on published similar work (Cohen et al, 2015;Han et al, 2013;Huggins et al, 2016;Li et al, 2011;Sebe-Pedros et al, 2016). AqATF4 peaks were also detected using the Peakzilla software (Bardet et al, 2013) relative to input DNA (-c 2 -s 3).…”

Section: Chip-seq Data Analysesmentioning

confidence: 99%

“…Another peak-caller, Peakzilla (Bardet et al, 2013), identified 814 peaks, 80% of which belonged to the MACS2 peak sets. Manual inspection of the read coverage tracks of the Peakzilla peaks that were not identified using MACS2 showed a relatively poor enrichment for AqATF4 in those regions and suggested that the peakzilla parameters chosen were not optimal.…”

Section: Aqatf4 Occupancy Is Not Promoter-proximalmentioning

confidence: 99%

Exploring the bZIP regulatory network in the sponge Amphimedon queenslandica: insights into the ancestral animal regulatory genome

Jindrich¹

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What genomic innovations supported the emergence of multicellular animals, over 600 million years ago, remains one of the most fundamental questions in evolutionary biology. Increasing evidence suggests that the elaboration of the regulatory mechanisms controlling gene expression, rather than gene innovation, underlies this transition. Since transcriptional regulation is largely achieved through the binding of specific transcription factors to specific cis-regulatory DNA, understanding the early evolution of these master orchestrators is key to retracing the origin of animals (metazoans). Basic leucine zipper (bZIP) transcription factors constitute one of the most ancient and conserved families of transcriptional regulators. They play a pivotal role in multiple pathways that regulate cell decisions and behaviours in all kingdoms of life. Here, I explore the early evolution and putative roles of bZIPs in a representative of one of the oldest surviving animal phyla, the marine sponge Amphimedon queenslandica.Using recently sequenced genomes from across the Eukaryota, and in particular the Metazoa, I first reconstruct the evolution of bZIPs, and document that this transcription factor superfamily has undergone multiple independent kingdom-level expansions. I present here a thorough analysis of the whole superfamily of bZIP transcription factors across the main eukaryotic clades and the putative bZIP network that was in place in the ancestor of all extant animals. To then explore the putative role of bZIP transcription factors in the metazoan ancestor, I identify the bZIP complement in the demosponge Amphimedon queenslandica (phylum Porifera). As expected for regulatory molecules, a majority of the 17 A. queenslandica bZIPs display high temporal specificity, cell-type specific localisation and are dynamically expressed throughout development. Along with bZIPs high expression across developmental stages, these characteristics point towards bZIPs having a fundamental role in this sponge. Given the consistent central role of these transcription factors in the functioning of extant animals, I infer that were already integrated in developmental and cell specific regulatory networks in the ancestral regulatory genome and supported the emergence of multicellularity.The PAR and ATF4 orthologues particularly stand out: they are highly expressed throughout Amphimedon life cycle and peak in expression at key developmental transitions. A. queenslandica PAR-bZIP AqPARa is part of the sponge circadian network. In this thesis, I establish that AqPARa is both spatially and temporally co-expressed with A. queenslandica cryptochrome AqCRY2, and that expression of both genes is entrained by light. I also explore the involvement of circadian genes that are conserved in other phyla in A. queenslandica response to light. This work provides insights III on the animal ancestral circadian regulatory network, and the evolution of PAR-bZIPs implication in the regulation of environmentally cued behaviours.A. queenslandica ATF4 ortholog...

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Identification of transcription factor binding sites from ChIP-seq data at high resolution

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 64 publications

References 44 publications

Evolutionary conservation of the eumetazoan gene regulatory landscape

Evolutionary conservation of the eumetazoan gene regulatory landscape

CexoR: an R/Bioconductor package to uncover high-resolution protein-DNA interactions in ChIP-exo replicates

Exploring the bZIP regulatory network in the sponge Amphimedon queenslandica: insights into the ancestral animal regulatory genome

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