Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Explicit DNase sequence bias modeling enables high resolution transcription factor footprint detection

ABSTRACT: DNase I footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. A number of computational approaches have been developed to accurately identify DNase-seq footprints and these methods have been used as a predictor of TF-DNA interactions by itself or in combination with other epigenetic features. However, recent studies have pointed to a substantial cleavage bias of DNase and its impact on footprinting, casting doubts on its predictive performance. To assess the potential for using DNaseI to identify individual binding sites, we performed DNase-seq experiments on deproteinized naked genomic DNA isolated from two different cell types and determined sequence cleavage bias associated with the DNase-seq protocol. This allowed us to build cleavage bias corrected footprint models specific to individual transcription factors. The predictive performance of these DNase-seq-based binding site models demonstrated that predicted footprints corresponded to high confidence TF-DNA interactions. To quantify the DNase I sequence-dependent cleavage bias, we performed DNase-seq experiments using deproteinized DNA from K562 and MCF7 cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Christopher Frank

PROVIDER: E-GEOD-61105 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Explicit DNase sequence bias modeling enables high resolution transcription factor footprint detection

Project description:DNase I footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. A number of computational approaches have been developed to accurately identify DNase-seq footprints and these methods have been used as a predictor of TF-DNA interactions by itself or in combination with other epigenetic features. However, recent studies have pointed to a substantial cleavage bias of DNase and its impact on footprinting, casting doubts on its predictive performance. To assess the potential for using DNaseI to identify individual binding sites, we performed DNase-seq experiments on deproteinized naked genomic DNA isolated from two different cell types and determined sequence cleavage bias associated with the DNase-seq protocol. This allowed us to build cleavage bias corrected footprint models specific to individual transcription factors. The predictive performance of these DNase-seq-based binding site models demonstrated that predicted footprints corresponded to high confidence TF-DNA interactions.

2014-09-04 | GSE61105 | GEO

Reproducible inference of transcription factor footprints in ATAC-seq and DNase-seq datasets via protocol-specific bias modeling

Project description:DNase-seq and ATAC-seq are broadly used methods to assay open chromatin regions genome-wide. The single nucleotide resolution of DNase-seq has been further exploited to infer transcription factor binding sites (TFBS) in regulatory regions via footprinting. Recent studies have demonstrated the sequence bias of DNase I and its adverse effects on footprinting efficiency. However, footprinting and the impact of sequence bias have not been extensively studied for ATAC-seq. Here, we undertake a systematic comparison of the two methods and show that a modification to the ATAC-seq protocol increases its yield and its agreement with DNase-seq data from the same cell line. We demonstrate that the two methods have distinct sequence biases and correct for these protocol-specific biases when performing footprinting. Despite differences in footprint shapes, the locations of the inferred footprints in ATAC-seq and DNase-seq are largely concordant. However, the protocol-specific sequence biases in conjunction with the sequence content of TFBSs impacts the discrimination of footprint from background, which leads to one method outperforming the other for some TFs. Finally, we address the depth required for reproducible identification of open chromatin regions and TF footprints.

2018-11-23 | GSE108513 | GEO

Conservation of mouse-human trans-regulatory circuitry despite high cis-regulatory divergence

Project description:The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining ~8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is ~95% similar with that derived from human TF footprints. However, only ~20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity. We performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining ~8.6 million transcription factor (TF) occupancy sites at nucleotide resolution.

2014-11-19 | E-GEOD-51341 | biostudies-arrayexpress

Genome-wide discovery of active regulatory elements and transcription factor footprints in Caenorhabditis elegans using DNase-seq

Project description:Deep sequencing of size-selected DNaseI-treated chromatin (DNase-seq) allows high resolution measurement of chromatin accessibility to DNaseI cleavage, permitting identification of de novo active cis regulatory modules (CRMs) and individual transcription factor (TF) binding sites. We adapted DNase-seq to nuclei isolated from C. elegans embryos and L1 arrest larvae to generate high-resolution maps of TF binding. Over half of embryonic DNaseI hypersensitive sites (DHS) were annotated in noncoding sequences, with 23% in intergenic, 11% promoter regions and 21% in introns, with similar statistics in data collected from L1 arrest larvae. Noncoding DHS exhibit high evolutionary sequence conservation and are enriched in marks of enhancer activity and transcription. We validated noncoding DHS against a previously investigated set of enhancers from myo-2, myo-3, hlh-1, elt-2 and lin-26/lir-1 gene loci and recapitulated 15 of 17 known enhancers in these loci. We then mined the DNase-seq data to identify putative active CRMs and TF footprints. Our DNase-seq data could also be used to improve predictions of tissue-specific expression compared to motifs alone. In a pilot functional test, 10 of 15 DHS from pha-4, icl-1 and ceh-13 drove reporter gene expression in transgenic C. elegans. Overall, we provide experimental annotation of 26,644 putative CRMs in the embryo containing 55,890 TF footprints, and 15,841 putative CRMs in the L1 arrest larvae containing 32,685 TF footprints.

2017-08-01 | GSE97425 | GEO

Mapping and dynamics of regulatory DNA and transcription factor networks in A. thaliana

Project description:We mapped DNaseI hypersensitive sites (DHSs) and applied genomic footprinting to define in vivo transcription factor (TF) occupancy at nucleotide resolution across the A. thaliana genome in whole seedlings during heat- and light-response states. We find that trait-associated variation localizes within DHSs, and that extensive TF occupancy within protein-coding exons has shaped A. thaliana codon usage. Analysis of >700,000 TF footprints disclosed an extensive cis-regulatory lexicon, and enabled construction of large-scale TF cross-regulatory networks. Although the cis- and trans-regulatory repertoire is markedly distinct from mammals, the architecture of A. thaliana TF networks is strikingly similar to those of human. Analysis of the DHS landscape and TF network dynamics during heat shock and photomorphogenesis revealed thousands of conditionally-sensitive elements and enabled mapping of key regulatory circuits. Our results provide an extensive resource for understanding and enabling diverse aspects of A. thaliana biology. Chromatin accessibility profiling (Dnase I-seq) and RNA-seq of 7-day-old dark-grown seedlings exposed to 0hr light, 30min light, 3hr light or 24hr LD conditions. Chromatin accessibility profiling (Dnase I-seq) and RNA-seq of 7-day-old LD-grown seedlings treated with a brief sever heat shock or kept under control conditions. Replicates are included when available; controls and read-normalized samples (samples that were subsampled to the same read-depth) are also included here.

2013-12-15 | E-GEOD-53322 | biostudies-arrayexpress

Conservation of mouse-human trans-regulatory circuitry despite high cis-regulatory divergence

2014-11-19 | GSE51341 | GEO

DNase I hypersensitivity and algorithmic prediction of TF binding in early pancreatic mES directed differentiation

Project description:This dataset uses DNase-seq to profile the genome-wide DNase I hypersensitivity of mES and mES-derived cells along an early pancreatic lineage and provides the locations of putative Transcription Factor (TF) binding sites using the PIQ algorithm. DNase-seq takes advantage of the preferential cutting of DNase I in open chromatin and steric blockage of of DNase I by tightly bound TFs that protect associated genomic DNA sequences. After deep sequencing of DNase I–digested genomic DNA from intact nuclei, genome-wide data on chromatin accessibility as well as TF-specific DNase I protection profiles that reveal the genomic binding locations of a majority of TFs are obtained. Such TF signature ‘DNase profiles’ reflect the effect of the TF on DNA shape and local chromatin architecture, extending hundreds of base pairs from a TF binding site, and these profiles are centered on ‘DNase footprints’ at the binding motif itself, which reflects the biophysics of protein-DNA binding. An algorithm, PIQ, is then applied that models the specific profile of each factor, and in combination with sequence information predicts the likely binding locations of over 700 TFs genome wide.

2014-01-19 | GSE53776 | GEO

Multi-scale chromatin footprinting reveals wide-spread alterations to the structure of DNA regulatory elements [Human BMMC ATAC]

Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.

2023-03-29 | GSE216462 | GEO

Multi-scale chromatin footprinting reveals wide-spread alterations to the structure of DNA regulatory elements [Human BMMC RNA]

2023-03-29 | GSE216461 | GEO

Multi-scale chromatin footprinting reveals wide-spread alterations to the structure of DNA regulatory elements [scATAC]

2023-03-29 | GSE216406 | GEO