STREME: accurate and versatile sequence motif discovery

Bioinformatics, Год журнала: 2021, Номер 37(18), С. 2834 - 2840

Опубликована: Март 23, 2021

Abstract Motivation Sequence motif discovery algorithms can identify novel sequence patterns that perform biological functions in DNA, RNA and protein sequences—for example, the binding site motifs of DNA- RNA-binding proteins. Results The STREME algorithm presented here advances state-of-the-art ab initio terms both accuracy versatility. Using vivo DNA (ChIP-seq) (CLIP-seq) data, validating with reference derived from vitro we show is more accurate, sensitive thorough than several widely used (DREME, HOMER, MEME, Peak-motifs) two other representative (ProSampler Weeder). STREME’s capabilities include ability to find datasets hundreds thousands sequences, short long (from 3 30 positions), differential pairs datasets, sequences over virtually any alphabet (DNA, RNA, user-defined alphabets). Unlike most algorithms, reports a useful estimate statistical significance each it discovers. easy use individually via its web server or command line, completely integrated MEME Suite analysis tools. name stands for ‘Simple, Thorough, Rapid, Enriched Motif Elicitation’. Availability implementation source code are provided freely non-commercial at http://meme-suite.org. Supplementary information data available Bioinformatics online.

Язык: Английский

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Metal binding properties, stability and reactivity of zinc fingers

Coordination Chemistry Reviews, Год журнала: 2018, Номер 367, С. 18 - 64

Опубликована: Апрель 27, 2018

Zinc fingers (ZFs) are among the most structurally diverse protein domains. They interact with nucleic acids, other proteins and lipids to facilitate a multitude of biological processes. Currently, there more than 10 known classes ZFs, various architectures, metal binding modes, functions reactivity. The versatility, selectivity stability these short amino acid sequences is achieved mainly by (i) residues participating in Zn(II) coordination (mostly Cys His), (ii) hydrophobic core ZF structure formation, (iii) variable responsible for inter- intramolecular interactions. Since their discovery, ZFs have been extensively studied terms structure, recognition targets application methodologies. Studies based on interactions ions complexes contributed understanding chemical properties discovery new types complexes, such as gold or lead fingers. Moreover, due presence nucleophilic thiolates, reactive oxygen nitrogen species well alkylating agents. Interactions many molecules disturb native site which further result structural functional damage ZFs. post-translational modifications including phosphorylation, acetylation, methylation nitrosylation frequently affect function via changes dynamics. Even though literature replete data regarding classical (ββα) still huge gap knowledge physicochemical reactivity types. In this review, factors that modulate reviewed. These include biogenic toxic occurring upon reaction species, methodology used characterization, aspects related chemistry.

Язык: Английский

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Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes

Annual Review of Cell and Developmental Biology, Год журнала: 2019, Номер 35(1), С. 357 - 379

Опубликована: Июль 8, 2019

Eukaryotic transcription factors (TFs) from the same structural family tend to bind similar DNA sequences, despite ability of these TFs execute distinct functions in vivo. The cell partly resolves this specificity paradox through combinatorial strategies and use low-affinity binding sites, which are better able distinguish between TFs. However, because sites have low affinity, it is challenging understand how recognize them Here, we summarize recent findings technological advancements that allow for quantification mechanistic interpretation TF recognition across a wide range affinities. We propose model integrates insights fields genetics biology provide further conceptual understanding specificity. argue eukaryotes, target driven by an inhomogeneous 3D nuclear distribution variation affinity such locally elevated concentration allows be functional.

Язык: Английский

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Linking the key physiological functions of essential micronutrients to their deficiency symptoms in plants

New Phytologist, Год журнала: 2024, Номер 242(3), С. 881 - 902

Опубликована: Март 3, 2024

Summary In this review, we untangle the physiological key functions of essential micronutrients and link them to deficiency responses in plants. Knowledge these at mechanistic level, resulting symptoms, have improved over last decade it appears timely review recent insights for each them. A proper understanding links between function symptom is indispensable an accurate identification nutritional disorders, thereby informing design development sustainable fertilization strategies. Similarly, knowledge molecular will be important breeding programmes aiming develop new crop genotypes with nutrient‐use efficiency resilience face changing soil climate conditions.

Язык: Английский

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In Utero Heat Stress Alters the Offspring Epigenome

Scientific Reports, Год журнала: 2018, Номер 8(1)

Опубликована: Сен. 26, 2018

Abstract Exposure to intrauterine heat stress during late gestation affects offspring performance into adulthood. However, underlying mechanistic links between thermal insult in fetal life and postnatal outcomes are not completely understood. We examined morphology, DNA methylation, gene expression of liver mammary gland for bull calves heifers that were gestated under maternal conditions or cooling (i.e. utero stressed vs . cooled calves). Mammary tissue was harvested from dairy their first lactation at birth. The contained more cells the glands comprised smaller alveoli. identified than 1,500 CpG sites differently methylated treatment groups. These CpGs associated with approximately 400 genes, which play a role processes, such as development , innate immune defense, cell signaling transcription translation also over 100 differentially expressed genes similar functions. Interestingly, fifty shared by both calf heifer gland. Intrauterine alters methylation profile programs morphology life, may contribute poorer calves.

Язык: Английский

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Transcription factor control of virulence in phytopathogenic fungi

Molecular Plant Pathology, Год журнала: 2021, Номер 22(7), С. 858 - 881

Опубликована: Май 11, 2021

Plant-pathogenic fungi are a significant threat to economic and food security worldwide. Novel protection strategies required therefore it is critical we understand the mechanisms by which these pathogens cause disease. Virulence factors pathogenicity genes have been identified, but in many cases their roles remain elusive. It becoming increasingly clear that gene regulation vital enable plant infection transcription play an essential role. Efforts determine regulatory functions plant-pathogenic expanded since annotation of fungal genomes revealed ubiquity from broad range families. This review establishes significance as elements provides systematic overview those functionally characterized. Detailed analysis provided on regulators well-characterized families controlling various aspects metabolism, development, stress tolerance, production virulence such effectors secondary metabolites. covers conserved with either specialized or nonspecialized roles, well recently identified targeting key pathways. Fundamental knowledge factor avenues identify novel improve our understanding networks linked pathogen evolution, while can themselves be specifically targeted for disease control. Areas requiring further insight regarding molecular and/or specific classes direction future investigation presented.

Язык: Английский

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PARIS induced defects in mitochondrial biogenesis drive dopamine neuron loss under conditions of parkin or PINK1 deficiency

Molecular Neurodegeneration, Год журнала: 2020, Номер 15(1)

Опубликована: Март 5, 2020

Mutations in PINK1 and parkin cause autosomal recessive Parkinson's disease (PD). Evidence placing common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent dopamine neuron degeneration PD lacking. Although are known regulate mitophagy, emerging data suggest that defects mitophagy unlikely be pathological relevance. Mitochondrial functions also tied their proteasomal regulation substrates. In this study, we examined how mediated the pathogenic substrate PARIS impacts dopaminergic network homeostasis neuronal survival Drosophila.The UAS-Gal4 system was employed for cell-type expression various transgenes. Effects on function were assessed by anti-TH immunostaining negative geotaxis assays. effects probed quantitative analysis mito-GFP labeled mitochondria, assessment abundance neurons isolated Fluorescence Activated Cell Sorting (FACS) qRT-PCR factors promote biogenesis. Statistical analyses two-tailed Student's T-test, one-way or two-way ANOVA as required considered significant when P < 0.05.We show biogenesis drive adult onset progressive loss motor deficits Drosophila models insufficiency. Such result from repression PGC-1α its downstream transcription NRF1 TFAM cooperatively Dopaminergic accumulation human recapitulates these neurodegenerative phenotypes effectively reversed PINK1, overexpression vivo. To our knowledge, only co-substrate specifically accumulate DA neurodegeneration locomotor stemming disrupted signaling.Our findings identify a highly conserved role promoting health via PARIS/ axis. The described here recapitulate cardinal thus will facilitate identification novel regulators physiologically relevant therapeutic interventions.

Язык: Английский

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Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis

Cell, Год журнала: 2022, Номер 185(12), С. 2148 - 2163.e27

Опубликована: Май 17, 2022

Язык: Английский

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Transposable elements drive the evolution of metazoan zinc finger genes

Genome Research, Год журнала: 2023, Номер 33(8), С. 1325 - 1339

Опубликована: Авг. 1, 2023

Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by rapid expansion contraction numerous subfamilies across animal phylogeny. The forces mechanisms underlying remain poorly understood, but there growing evidence that, tetrapods, targeting repression lineage-specific transposable elements (TEs) plays a critical role Krüppel-associated box (KZNF) subfamily. Currently, it unknown whether this function coevolutionary relationship unique to KZNFs or broader feature metazoan ZNFs. Here, we present that genomic conflict with TEs has been central driver diversification ZNFs animals. Sampling from 3221 genome assemblies, show copy number retroelements correlates at least 750 million years evolution. Using computational predictions, preferentially bind diverse species. We further investigate subfamily found cyprinid fish, which conserved sequence dubbed fish N-terminal finger–associated (FiNZ) domain. Zebrafish possess approximately 700 FiNZ-ZNFs, many are evolving adaptively under positive selection. Like mammalian KZNFs, most zebrafish FiNZ-ZNFs expressed onset zygotic activation, blocking their translation using morpholinos during early embryogenesis results derepression transcriptionally active TEs. Together, these data suggest intimately connected TE throughout

Язык: Английский

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Updated understanding of the protein–DNA recognition code used by C2H2 zinc finger proteins

Current Opinion in Structural Biology, Год журнала: 2024, Номер 87, С. 102836 - 102836

Опубликована: Май 15, 2024

C2H2 zinc-finger (ZF) proteins form the largest family of DNA-binding transcription factors coded by mammalian genomes. In a typical ZF module, there are twelve residues (numbered from -1 to -12) between last zinc-coordinating cysteine and first histidine. The established C2H2-ZF "recognition code" suggests that at positions -1, -4, -7 recognize 5', central, 3' bases DNA base-pair triplet, respectively. Structural studies have highlighted additional -5 -8 also play roles in specific recognition. presence bulky either charged or polar these five determines specificity for given bases: guanine is recognized arginine, lysine, histidine; adenine asparagine glutamine; thymine 5-methylcytosine glutamate; unmodified cytosine aspartate. This review discusses recent structural characterizations C2H2-ZFs add our understanding principles underlying recognition code.

Язык: Английский

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