JASPAR 2020: update of the open-access database of transcription factor binding profiles

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: unknown

Published: Oct. 16, 2019

Abstract JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release JASPAR, the CORE collection has been expanded with 245 new PFMs (169 vertebrates, 42 plants, 17 nematodes, 10 insects, and 7 fungi), 156 were updated (125 28 plants 3 insects). These represent 18% expansion compared to previous release. 2020 comes a novel unvalidated TF-binding which our curators did not find orthogonal supporting evidence literature. This dedicated web form engage community curation profiles. Moreover, we created Q&A forum ease communication between user curators. Finally, genomic tracks, inference tool, profile similarity clusters. All data available through website, its associated RESTful API, JASPAR2020 R/Bioconductor package.

Language: Английский

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JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D174 - D182

Published: Nov. 14, 2023

JASPAR (https://jaspar.elixir.no/) is a widely-used open-access database presenting manually curated high-quality and non-redundant DNA-binding profiles for transcription factors (TFs) across taxa. In this 10th release 20th-anniversary update, the CORE collection has expanded with 329 new profiles. We updated three existing provided orthogonal support 72 from previous release's UNVALIDATED collection. Altogether, 2024 update provides 20% increase in release. A trimming algorithm enhanced by removing low information content flanking base pairs, which were likely uninformative (within capacity of PFM models) TFBS predictions modelling TF-DNA interactions. This includes metadata, featuring refined classification plant TFs' structural domains. The collections prompt updates to genomic tracks predicted TF binding sites (TFBSs) 8 organisms, human mouse available as native UCSC Genome browser. All data are through web interface programmatically its API Bioconductor pyJASPAR packages. Finally, extraction tool enables users retrieve TFBSs intersecting their regions interest.

Language: Английский

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DNA methylation disruption reshapes the hematopoietic differentiation landscape

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(4), P. 378 - 387

Published: March 23, 2020

Language: Английский

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Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 8, 2024

Abstract Background Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription can distinguish between unmodified and modified bases. Current models of factor binding tend not take modifications into account, while the recent few that do often have limitations. This makes a comprehensive accurate profiling affinities difficult. Results Here, we develop methods identify sites DNA. Our expand standard /// alphabet include cytosine modifications. We Cytomod create genomic sequences also enhance MEME Suite, adding capacity handle custom alphabets. adapt well-established position weight matrix (PWM) model affinity this expanded alphabet. Using these methods, modification-sensitive motifs. confirm established preferences, such as preference ZFP57 C/EBPβ for methylated motifs c-Myc unmethylated E-box Conclusions known preferences tune parameters, discover novel wide array factors. Finally, validate our predictions OCT4 using cleavage under targets release nuclease (CUT&RUN) experiments across conventional, methylation-, hydroxymethylation-enriched sequences. approach readily extends other As more genome-wide single-base resolution modification data becomes available, expect method will yield insights altered many different

Language: Английский

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Epigenomic insights into common human disease pathology

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: April 11, 2024

Abstract The epigenome—the chemical modifications and chromatin-related packaging of the genome—enables same genetic template to be activated or repressed in different cellular settings. This multi-layered mechanism facilitates cell-type specific function by setting local sequence 3D interactive activity level. Gene transcription is further modulated through interplay with factors co-regulators. human body requires this epigenomic apparatus precisely installed throughout development then adequately maintained during lifespan. causal role epigenome pathology, beyond imprinting disorders tumour suppressor genes, was brought into spotlight large-scale sequencing projects identifying that mutations machinery genes could critical drivers both cancer developmental disorders. Abrogation providing new molecular insights pathogenesis. However, deciphering full breadth implications these changes remains challenging. Knowledge accruing regarding disease mechanisms clinical biomarkers, pathogenically relevant surrogate tissue analyses, respectively. Advances include consortia generated reference epigenomes, high-throughput DNA methylome association studies, as well ageing-related diseases from biological ‘clocks’ constructed machine learning algorithms. Also, 3rd-generation beginning disentangle complexity modification haplotypes. Cell-free methylation a biomarker has clear utility potential assess organ damage across many Finally, understanding aetiology brings it opportunity for exact therapeutic alteration CRISPR-activation inhibition.

Language: Английский

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DNAmod: the DNA modification database

Journal of Cheminformatics, Journal Year: 2019, Volume and Issue: 11(1)

Published: April 23, 2019

Covalent DNA modifications, such as 5-methylcytosine (5mC), are increasingly the focus of numerous research programs. In eukaryotes, both 5mC and 5-hydroxymethylcytosine (5hmC) now recognized stable epigenetic marks, with diverse functions. Bacteria, archaea, viruses contain various other modified nucleobases. Numerous databases describe RNA histone but no database specifically catalogues despite their broad importance in regulation. To address this need, we have developed DNAmod: modification database. DNAmod is an open-source ( https://dnamod.hoffmanlab.org ) that modifications provides a single source to learn about properties. web interface easily browse search through these modifications. The annotates chemical properties structures all curated bases, much larger list candidate entities. includes manual annotations available sequencing methods, descriptions occurrence nature, existing suggested nomenclature. enables researchers rapidly review previous work, select mapping techniques, track recent developments concerning bases interest.

Language: Английский

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Sequence and chromatin determinants of transcription factor binding and the establishment of cell type-specific binding patterns

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Journal Year: 2019, Volume and Issue: 1863(6), P. 194443 - 194443

Published: Oct. 19, 2019

Language: Английский

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Widespread effects of DNA methylation and intra-motif dependencies revealed by novel transcription factor binding models

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(18), P. e95 - e95

Published: Aug. 31, 2023

Several studies suggested that transcription factor (TF) binding to DNA may be impaired or enhanced by methylation. We present MeDeMo, a toolbox for TF motif analysis combines information about methylation with models capturing intra-motif dependencies. In large-scale study using ChIP-seq data 335 TFs, we identify novel TFs show behaviour associated Overall, find the presence of CpG decreases likelihood majority methylation-associated TFs. For considerable subset dependencies are pivotal accurately modelling impact on binding. illustrate methylation-aware allow predict differential peaks and improve genome-wide Our work indicates simplistic neglect effect lead systematic underperformance

Language: Английский

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Targeting Gene Transcription Prevents Antibiotic Resistance

Antibiotics, Journal Year: 2025, Volume and Issue: 14(4), P. 345 - 345

Published: March 27, 2025

Innovative strategies are needed to curb the global health challenge of antibiotic resistance. The World Health Organization predicts that resistance could lead millions deaths annually. Pharmaceutical experience has shown modest alterations commonly-used broad-spectrum antibiotics readily elicit resistant strains. Thus, continued simple iterative improvements on current not sustainable. Traditional target single sites with goal a antibiotic. In comparison, novel strategy targets multiple in single- or multidrug-resistant Gram-positive bacterial pathogens. objective is exploit mechanisms by which pathogenic bacteria require genes for transcriptional regulation. Transcription regulatory factors can be manipulated and their functions disrupted hamper viability. Some transcription regulate one more steps metabolic pathways. always proteins; some small-molecule metabolites triggering genetic through riboswitches, others RNAs. Novel agents have been discovered computer-simulated docking an unusual site nascent mRNA. These compounds exhibit innovative chemistries modes action inhibit growth binding blocking critical mRNA functions. tRNA-dependent regulation amino acid metabolism illustrates possibilities antibiotic-resistant thwart emergence

Language: Английский

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Effects of DNA Methylation on TFs in Human Embryonic Stem Cells

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 23, 2021

DNA methylation is an important epigenetic mechanism for gene regulation. The conventional view of that could disrupt protein-DNA interactions and repress expression. Several recent studies reported alter transcription factors (TFs) binding sequence specificity in vitro . Here, we took advantage the large sets ChIP-seq data TFs whole-genome bisulfite sequencing many cell types to perform a systematic analysis vivo We observed bind methylated regions, especially H1-hESC cells. By locating sites, confirmed some CpGs directly. different proportion at TF motifs statuses shows are sensitive with motifs, such as CEBPB CTCF. At same time, interactively local methylation. hypermethylation sites extensively overlap enhancers. And also found DNase I hypersensitive were specifically hypermethylated last, compared TFs’ regions multiple types, CTCF high not conservative. These pieces evidence indicate cells may associate enhancers regulate special biological functions.

Language: Английский

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