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1.
PLoS One ; 19(5): e0295971, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709794

RESUMO

The human genome is pervasively transcribed and produces a wide variety of long non-coding RNAs (lncRNAs), constituting the majority of transcripts across human cell types. Some specific nuclear lncRNAs have been shown to be important regulatory components acting locally. As RNA-chromatin interaction and Hi-C chromatin conformation data showed that chromatin interactions of nuclear lncRNAs are determined by the local chromatin 3D conformation, we used Hi-C data to identify potential target genes of lncRNAs. RNA-protein interaction data suggested that nuclear lncRNAs act as scaffolds to recruit regulatory proteins to target promoters and enhancers. Nuclear lncRNAs may therefore play a role in directing regulatory factors to locations spatially close to the lncRNA gene. We provide the analysis results through an interactive visualization web portal at https://fantom.gsc.riken.jp/zenbu/reports/#F6_3D_lncRNA.


Assuntos
Cromatina , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cromatina/metabolismo , Cromatina/genética , Humanos , Anotação de Sequência Molecular , Núcleo Celular/metabolismo , Núcleo Celular/genética , Genoma Humano , Regiões Promotoras Genéticas
2.
Nucleic Acids Res ; 52(D1): D154-D163, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37971293

RESUMO

We present a major update of the HOCOMOCO collection that provides DNA binding specificity patterns of 949 human transcription factors and 720 mouse orthologs. To make this release, we performed motif discovery in peak sets that originated from 14 183 ChIP-Seq experiments and reads from 2554 HT-SELEX experiments yielding more than 400 thousand candidate motifs. The candidate motifs were annotated according to their similarity to known motifs and the hierarchy of DNA-binding domains of the respective transcription factors. Next, the motifs underwent human expert curation to stratify distinct motif subtypes and remove non-informative patterns and common artifacts. Finally, the curated subset of 100 thousand motifs was supplied to the automated benchmarking to select the best-performing motifs for each transcription factor. The resulting HOCOMOCO v12 core collection contains 1443 verified position weight matrices, including distinct subtypes of DNA binding motifs for particular transcription factors. In addition to the core collection, HOCOMOCO v12 provides motif sets optimized for the recognition of binding sites in vivo and in vitro, and for annotation of regulatory sequence variants. HOCOMOCO is available at https://hocomoco12.autosome.org and https://hocomoco.autosome.org.


Assuntos
Bases de Dados Genéticas , Regulação da Expressão Gênica , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição , Animais , Humanos , Camundongos , Sítios de Ligação/genética , Motivos de Nucleotídeos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Internet , Domínios e Motivos de Interação entre Proteínas/genética
3.
Nat Commun ; 14(1): 1258, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36878908

RESUMO

Neural crest cells are highly multipotent stem cells, but it remains unclear how their fate restriction to specific fates occurs. The direct fate restriction model hypothesises that migrating cells maintain full multipotency, whilst progressive fate restriction envisages fully multipotent cells transitioning to partially-restricted intermediates before committing to individual fates. Using zebrafish pigment cell development as a model, we show applying NanoString hybridization single cell transcriptional profiling and RNAscope in situ hybridization that neural crest cells retain broad multipotency throughout migration and even in post-migratory cells in vivo, with no evidence for partially-restricted intermediates. We find that leukocyte tyrosine kinase early expression marks a multipotent stage, with signalling driving iridophore differentiation through repression of fate-specific transcription factors for other fates. We reconcile the direct and progressive fate restriction models by proposing that pigment cell development occurs directly, but dynamically, from a highly multipotent state, consistent with our recently-proposed Cyclical Fate Restriction model.


Assuntos
Condução de Veículo , Peixe-Zebra , Animais , Peixe-Zebra/genética , Células-Tronco Hematopoéticas , Células-Tronco Multipotentes , Diferenciação Celular/genética
4.
F1000Res ; 11: 33, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811788

RESUMO

The position weight matrix, also called the position-specific scoring matrix, is the commonly accepted model to quantify the specificity of transcription factor binding to DNA. Position weight matrices are used in thousands of projects and software tools in regulatory genomics, including computational prediction of the regulatory impact of single-nucleotide variants. Yet, recently Yan et al. reported that "the position weight matrices of most transcription factors lack sufficient predictive power" if applied to the analysis of regulatory variants studied with a newly developed experimental method, SNP-SELEX. Here, we re-analyze the rich experimental dataset obtained by Yan et al. and show that appropriately selected position weight matrices in fact can adequately quantify transcription factor binding to alternative alleles.


Assuntos
Software , Fatores de Transcrição , Sítios de Ligação/genética , Matrizes de Pontuação de Posição Específica , Ligação Proteica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Nucleic Acids Res ; 50(W1): W51-W56, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35446421

RESUMO

We present ANANASTRA, https://ananastra.autosome.org, a web server for the identification and annotation of regulatory single-nucleotide polymorphisms (SNPs) with allele-specific binding events. ANANASTRA accepts a list of dbSNP IDs or a VCF file and reports allele-specific binding (ASB) sites of particular transcription factors or in specific cell types, highlighting those with ASBs significantly enriched at SNPs in the query list. ANANASTRA is built on top of a systematic analysis of allelic imbalance in ChIP-Seq experiments and performs the ASB enrichment test against background sets of SNPs found in the same source experiments as ASB sites but not displaying significant allelic imbalance. We illustrate ANANASTRA usage with selected case studies and expect that ANANASTRA will help to conduct the follow-up of GWAS in terms of establishing functional hypotheses and designing experimental verification.


Assuntos
Polimorfismo de Nucleotídeo Único , Fatores de Transcrição , Alelos , Sítios de Ligação , Estudo de Associação Genômica Ampla , Ligação Proteica , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA
6.
Biochim Biophys Acta Gene Regul Mech ; 1865(1): 194768, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34757206

RESUMO

As computational modeling becomes more essential to analyze and understand biological regulatory mechanisms, governance of the many databases and knowledge bases that support this domain is crucial to guarantee reliability and interoperability of resources. To address this, the COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together a wide range of experts from all over the world working on various steps in the knowledge management process that focuses on understanding gene regulatory mechanisms. The discussions between ontologists, curators, text miners, biologists, bioinformaticians, philosophers and computational scientists spawned a host of activities aimed to standardize and update existing knowledge management workflows and involve end-users in the process of designing the Gene Regulation Knowledge Commons (GRKC). Here the GREEKC consortium describes its main achievements in improving this GRKC.


Assuntos
Regulação da Expressão Gênica , Reprodutibilidade dos Testes
7.
Nat Commun ; 12(1): 2751, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980847

RESUMO

Sequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.


Assuntos
Alelos , Genoma Humano , Sequências Reguladoras de Ácido Nucleico/genética , Fatores de Transcrição/metabolismo , Cromatina/metabolismo , Bases de Dados Genéticas , Dosagem de Genes , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla , Humanos , Motivos de Nucleotídeos , Fenótipo , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Locos de Características Quantitativas
8.
Methods Mol Biol ; 2252: 269-294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765281

RESUMO

During translation, the rate of ribosome movement along mRNA varies. This leads to a non-uniform ribosome distribution along the transcript, depending on local mRNA sequence, structure, tRNA availability, and translation factor abundance, as well as the relationship between the overall rates of initiation, elongation, and termination. Stress, antibiotics, and genetic perturbations affecting composition and properties of translation machinery can alter the ribosome positional distribution dramatically. Here, we offer a computational protocol for analyzing positional distribution profiles using ribosome profiling (Ribo-Seq) data. The protocol uses papolarity, a new Python toolkit for the analysis of transcript-level short read coverage profiles. For a single sample, for each transcript papolarity allows for computing the classic polarity metric which, in the case of Ribo-Seq, reflects ribosome positional preferences. For comparison versus a control sample, papolarity estimates an improved metric, the relative linear regression slope of coverage along transcript length. This involves de-noising by profile segmentation with a Poisson model and aggregation of Ribo-Seq coverage within segments, thus achieving reliable estimates of the regression slope. The papolarity software and the associated protocol can be conveniently used for Ribo-Seq data analysis in the command-line Linux environment. Papolarity package is available through Python pip package manager. The source code is available at https://github.com/autosome-ru/papolarity .


Assuntos
Biologia Computacional/métodos , RNA Mensageiro/genética , Ribossomos/metabolismo , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Modelos Lineares , Distribuição de Poisson , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Software
9.
Nucleic Acids Res ; 49(D1): D104-D111, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33231677

RESUMO

The Gene Transcription Regulation Database (GTRD; http://gtrd.biouml.org/) contains uniformly annotated and processed NGS data related to gene transcription regulation: ChIP-seq, ChIP-exo, DNase-seq, MNase-seq, ATAC-seq and RNA-seq. With the latest release, the database has reached a new level of data integration. All cell types (cell lines and tissues) presented in the GTRD were arranged into a dictionary and linked with different ontologies (BRENDA, Cell Ontology, Uberon, Cellosaurus and Experimental Factor Ontology) and with related experiments in specialized databases on transcription regulation (FANTOM5, ENCODE and GTEx). The updated version of the GTRD provides an integrated view of transcription regulation through a dedicated web interface with advanced browsing and search capabilities, an integrated genome browser, and table reports by cell types, transcription factors, and genes of interest.


Assuntos
Bases de Dados Genéticas , Regulação da Expressão Gênica , Genoma , Fatores de Transcrição/genética , Transcrição Gênica , Animais , Linhagem Celular , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Ontologia Genética , Humanos , Internet , Camundongos , Anotação de Sequência Molecular , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Software , Fatores de Transcrição/classificação , Fatores de Transcrição/metabolismo
10.
BMC Genomics ; 21(1): 754, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138777

RESUMO

BACKGROUND: Efforts to elucidate the function of enhancers in vivo are underway but their vast numbers alongside differing enhancer architectures make it difficult to determine their impact on gene activity. By systematically annotating multiple mouse tissues with super- and typical-enhancers, we have explored their relationship with gene function and phenotype. RESULTS: Though super-enhancers drive high total- and tissue-specific expression of their associated genes, we find that typical-enhancers also contribute heavily to the tissue-specific expression landscape on account of their large numbers in the genome. Unexpectedly, we demonstrate that both enhancer types are preferentially associated with relevant 'tissue-type' phenotypes and exhibit no difference in phenotype effect size or pleiotropy. Modelling regulatory data alongside molecular data, we built a predictive model to infer gene-phenotype associations and use this model to predict potentially novel disease-associated genes. CONCLUSION: Overall our findings reveal that differing enhancer architectures have a similar impact on mammalian phenotypes whilst harbouring differing cellular and expression effects. Together, our results systematically characterise enhancers with predicted phenotypic traits endorsing the role for both types of enhancers in human disease and disorders.


Assuntos
Elementos Facilitadores Genéticos , Animais , Elementos Facilitadores Genéticos/genética , Humanos , Camundongos , Fenótipo
11.
Front Genet ; 10: 1078, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737053

RESUMO

Many problems of modern genetics and functional genomics require the assessment of functional effects of sequence variants, including gene expression changes. Machine learning is considered to be a promising approach for solving this task, but its practical applications remain a challenge due to the insufficient volume and diversity of training data. A promising source of valuable data is a saturation mutagenesis massively parallel reporter assay, which quantitatively measures changes in transcription activity caused by sequence variants. Here, we explore the computational predictions of the effects of individual single-nucleotide variants on gene transcription measured in the massively parallel reporter assays, based on the data from the recent "Regulation Saturation" Critical Assessment of Genome Interpretation challenge. We show that the estimated prediction quality strongly depends on the structure of the training and validation data. Particularly, training on the sequence segments located next to the validation data results in the "information leakage" caused by the local context. This information leakage allows reproducing the prediction quality of the best CAGI challenge submissions with a fairly simple machine learning approach, and even obtaining notably better-than-random predictions using irrelevant genomic regions. Validation scenarios preventing such information leakage dramatically reduce the measured prediction quality. The performance at independent regulatory regions entirely excluded from the training set appears to be much lower than needed for practical applications, and even the performance estimation will become reliable only in the future with richer data from multiple reporters. The source code and data are available at https://bitbucket.org/autosomeru_cagi2018/cagi2018_regsat and https://genomeinterpretation.org/content/expression-variants.

12.
Biomolecules ; 9(9)2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500189

RESUMO

Mitochondrial dysfunction and oxidative stress are likely involved in atherogenesis. Since the mitochondrial genome variation can alter functional activity of cells, it is necessary to assess the presence in atherosclerotic lesions of mitochondrial DNA (mtDNA) heteroplasmic mutations known to be associated with different pathological processes and ageing. In this study, mtDNA heteroplasmy and copy number (mtCN) were evaluated in the autopsy-derived samples of aortic intima differing by the type of atherosclerotic lesions. To detect mtDNA heteroplasmic variants, next generation sequencing was used, and mtCN measurement was performed by qPCR. It was shown that mtDNA heteroplasmic mutations are characteristic for particular areas of intimal tissue; in 83 intimal samples 55 heteroplasmic variants were found; mean minor allele frequencies level accounted for 0.09, with 12% mean heteroplasmy level. The mtCN variance measured in adjacent areas of intima was high, but atherosclerotic lesions and unaffected intima did not differ significantly in mtCN values. Basing on the ratio of minor and major nucleotide mtDNA variants, we can conclude that there exists the increase in the number of heteroplasmic mtDNA variants, which corresponds to the extent of atherosclerotic morphologic phenotype.


Assuntos
Aorta Abdominal/metabolismo , Aterosclerose/genética , DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Idoso de 80 Anos ou mais , Aorta Abdominal/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , DNA Mitocondrial/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
13.
PeerJ ; 7: e6554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863681

RESUMO

Recent research has indicated that in addition to the unique genotype each individual may also have a unique microbiota composition. Difference in microbiota composition may emerge from both its species and strain constituents. It is important to know the precise composition especially for the gut microbiota (GM), since it can contribute to the health assessment, personalized treatment, and disease prevention for individuals and groups (cohorts). The existing methods for species and strain composition in microbiota are not always precise and usually not so easy to use. Probiotic bacteria of the genus Bifidobacterium and Lactobacillus make an essential component of human GM. Previously we have shown that in certain Bifidobacterium and Lactobacillus species the RelBE and MazEF superfamily of toxin-antitoxin (TA) systems may be used as functional biomarkers to differentiate these groups of bacteria at the species and strain levels. We have composed a database of TA genes of these superfamily specific for all lactobacilli and bifidobacteria species with complete genome sequence and confirmed that in all Lactobacillus and Bifidobacterium species TA gene composition is species and strain specific. To analyze composition of species and strains of two bacteria genera, Bifidobacterium and Lactobacillus, in human GM we developed TAGMA (toxin antitoxin genes for metagenomes analyses) software based on polymorphism in TA genes. TAGMA was tested on gut metagenomic samples. The results of our analysis have shown that TAGMA can be used to characterize species and strains of Lactobacillus and Bifidobacterium in metagenomes.

14.
PeerJ ; 7: e6125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643692

RESUMO

Antimicrobial peptides (AMPs) are the main components of the plant innate immune system. Defensins represent the most important AMP family involved in defense and non-defense functions. In this work, global RNA sequencing and de novo transcriptome assembly were performed to explore the diversity of defensin-like (DEFL) genes in the wheat Triticum kiharae and to study their role in induced resistance (IR) mediated by the elicitor metabolites of a non-pathogenic strain FS-94 of Fusarium sambucinum. Using a combination of two pipelines for DEFL mining in transcriptome data sets, as many as 143 DEFL genes were identified in T. kiharae, the vast majority of them represent novel genes. According to the number of cysteine residues and the cysteine motif, wheat DEFLs were classified into ten groups. Classical defensins with a characteristic 8-Cys motif assigned to group 1 DEFLs represent the most abundant group comprising 52 family members. DEFLs with a characteristic 4-Cys motif CX{3,5}CX{8,17}CX{4,6}C named group 4 DEFLs previously found only in legumes were discovered in wheat. Within DEFL groups, subgroups of similar sequences originated by duplication events were isolated. Variation among DEFLs within subgroups is due to amino acid substitutions and insertions/deletions of amino acid sequences. To identify IR-related DEFL genes, transcriptional changes in DEFL gene expression during elicitor-mediated IR were monitored. Transcriptional diversity of DEFL genes in wheat seedlings in response to the fungus Fusarium oxysporum, FS-94 elicitors, and the combination of both (elicitors + fungus) was demonstrated, with specific sets of up- and down-regulated DEFL genes. DEFL expression profiling allowed us to gain insight into the mode of action of the elicitors from F. sambucinum. We discovered that the elicitors up-regulated a set of 24 DEFL genes. After challenge inoculation with F. oxysporum, another set of 22 DEFLs showed enhanced expression in IR-displaying seedlings. These DEFLs, in concert with other defense molecules, are suggested to determine enhanced resistance of elicitor-pretreated wheat seedlings. In addition to providing a better understanding of the mode of action of the elicitors from FS-94 in controlling diseases, up-regulated IR-specific DEFL genes represent novel candidates for genetic transformation of plants and development of pathogen-resistant crops.

15.
BMC Res Notes ; 11(1): 756, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30352610

RESUMO

OBJECTIVES: Mammalian genomics studies, especially those focusing on transcriptional regulation, require information on genomic locations of regulatory regions, particularly, transcription factor (TF) binding sites. There are plenty of published ChIP-Seq data on in vivo binding of transcription factors in different cell types and conditions. However, handling of thousands of separate data sets is often impractical and it is desirable to have a single global map of genomic regions potentially bound by a particular TF in any of studied cell types and conditions. DATA DESCRIPTION: Here we report human and mouse cistromes, the maps of genomic regions that are routinely identified as TF binding sites, organized by TF. We provide cistromes for 349 mouse and 599 human TFs. Given a TF, its cistrome regions are supported by evidence from several ChIP-Seq experiments or several computational tools, and, as an optional filter, contain occurrences of sequence motifs recognized by the TF. Using the cistrome, we provide an annotation of TF binding sites in the vicinity of human and mouse transcription start sites. This information is useful for selecting potential gene targets of transcription factors and detecting co-regulated genes in differential gene expression data.


Assuntos
Genoma , Análise de Sequência de DNA , Fatores de Transcrição , Animais , Sítios de Ligação , Humanos , Camundongos
16.
Curr Pharm Des ; 24(26): 3143-3151, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205792

RESUMO

BACKGROUND: A hallmark of atherosclerosis is its complex pathogenesis, which is dependent on altered cholesterol metabolism and inflammation. Both arms of pathogenesis involve myeloid cells. Monocytes migrating into the arterial walls interact with modified low-density lipoprotein (LDL) particles, accumulate cholesterol and convert into foam cells, which promote plaque formation and also contribute to inflammation by producing proinflammatory cytokines. A number of studies characterized transcriptomics of macrophages following interaction with modified LDL, and revealed alteration of the expression of genes responsible for inflammatory response and cholesterol metabolism. However, it is still unclear how these two processes are related to each other to contribute to atherosclerotic lesion formation. METHODS: We attempted to identify the main mater regulator genes in macrophages treated with atherogenic modified LDL using a bioinformatics approach. RESULTS: We found that most of the identified genes were involved in inflammation, and none of them was implicated in cholesterol metabolism. Among the key identified genes were interleukin (IL)-7, IL-7 receptor, IL- 15 and CXCL8. CONCLUSION: Our results indicate that activation of the inflammatory pathway is the primary response of the immune cells to modified LDL, while the lipid metabolism genes may be a secondary response triggered by inflammatory signalling.


Assuntos
Perfilação da Expressão Gênica , Inflamação/genética , Inflamação/metabolismo , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Voluntários Saudáveis , Humanos , Lipoproteínas LDL/química
17.
Exp Mol Pathol ; 105(2): 202-207, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30118702

RESUMO

High density lipoproteins (HDL) are key components of reverse cholesterol transport pathway. HDL removes excessive cholesterol from peripheral cells, including macrophages, providing protection from cholesterol accumulation and conversion into foam cells, which is a key event in pathogenesis of atherosclerosis. The mechanism of cellular cholesterol efflux stimulation by HDL involves interaction with the ABCA1 lipid transporter and ensuing transfer of cholesterol to HDL particles. In this study, we looked for additional proteins contributing to HDL-dependent cholesterol efflux. Using RNAseq, we analyzed mRNAs induced by HDL in human monocyte-derived macrophages and identified three genes, fatty acid desaturase 1 (FADS1), insulin induced gene 1 (INSIG1), and the low-density lipoprotein receptor (LDLR), expression of which was significantly upregulated by HDL. We individually knocked down these genes in THP-1 cells using gene silencing by siRNA, and measured cellular cholesterol efflux to HDL. Knock down of FADS1 did not significantly change cholesterol efflux (p = 0.70), but knockdown of INSIG1 and LDLR resulted in highly significant reduction of the efflux to HDL (67% and 75% of control, respectively, p < 0.001). Importantly, the suppression of cholesterol efflux was independent of known effects of these genes on cellular cholesterol content, as cells were loaded with cholesterol using acetylated LDL. These results indicate that HDL particles stimulate expression of genes that enhance cellular cholesterol transfer to HDL.


Assuntos
HDL-Colesterol/genética , Macrófagos/fisiologia , Transportador 1 de Cassete de Ligação de ATP/genética , Aterosclerose/fisiopatologia , Transporte Biológico , Colesterol , HDL-Colesterol/metabolismo , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Células Espumosas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Inativação Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipoproteínas HDL/genética , Lipoproteínas HDL/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , RNA Mensageiro , RNA Interferente Pequeno , Receptores de LDL/genética , Receptores de LDL/metabolismo , Células THP-1 , Regulação para Cima
18.
Mar Genomics ; 37: 18-20, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33250120

RESUMO

Gammaproteobacterium Thalassolituus oleivorans plays an important role in oil degradation in sea water through emulsifying crude oil and alkanes at low temperatures in polar sea environment. Here we report the complete genome sequence of K-188 strain (VKPM B-9394) isolated in the Barents Sea and compare it with other known Thalassolituus oleivorans strains. The Thalassolituus strains are differed in orthologs number of the genes of alkane degradation, transport proteins, genes of sugar utilization, endonucleases, signaling proteins, transcriptional regulators and presence of CRISPR/Cas locus. Also only the genome of K-188 contains the 3-hydroxyalkanoate synthetase.

19.
Nucleic Acids Res ; 46(D1): D252-D259, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29140464

RESUMO

We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences.


Assuntos
Bases de Dados Genéticas , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação/genética , Imunoprecipitação da Cromatina , Humanos , Camundongos , Modelos Genéticos , Motivos de Nucleotídeos , Análise de Sequência de DNA
20.
PLoS One ; 12(2): e0172681, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28234966

RESUMO

We studied functional effect of rs12722489 single nucleotide polymorphism located in the first intron of human IL2RA gene on transcriptional regulation. This polymorphism is associated with multiple autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative colitis). Analysis in silico suggested significant difference in the affinity of estrogen receptor (ER) binding site between alternative allelic variants, with stronger predicted affinity for the risk (G) allele. Electrophoretic mobility shift assay showed that purified human ERα bound only G variant of a 32-bp genomic sequence containing rs12722489. Chromatin immunoprecipitation demonstrated that endogenous human ERα interacted with rs12722489 genomic region in vivo and DNA pull-down assay confirmed differential allelic binding of amplified 189-bp genomic fragments containing rs12722489 with endogenous human ERα. In a luciferase reporter assay, a kilobase-long genomic segment containing G but not A allele of rs12722489 demonstrated enhancer properties in MT-2 cell line, an HTLV-1 transformed human cell line with a regulatory T cell phenotype.


Assuntos
Receptor alfa de Estrogênio/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Polimorfismo de Nucleotídeo Único , Elementos de Resposta , Linfócitos T Reguladores/metabolismo , Alelos , Sequência de Bases , Sítios de Ligação , Linhagem Celular Transformada , Imunoprecipitação da Cromatina , Ensaio de Desvio de Mobilidade Eletroforética , Receptor alfa de Estrogênio/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Íntrons , Luciferases/genética , Luciferases/metabolismo , Ligação Proteica , Linfócitos T Reguladores/citologia
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