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Pesquisa : G05.360.340.024.340.137.750 [Categoria DeCS]
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  1 / 1982 MEDLINE  
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[PMID]:29352242
[Au] Autor:Cottrell KA; Chaudhari HG; Cohen BA; Djuranovic S
[Ad] Endereço:Department of Cell Biology and Physiology, School of Medicine, Washington University, St. Louis, MO, 63110, USA.
[Ti] Título:PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs.
[So] Source:Nat Commun;9(1):301, 2018 01 19.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RNA binding proteins (RBP) and microRNAs (miRNAs) often bind sequences in 3' untranslated regions (UTRs) of mRNAs, and regulate stability and translation efficiency. With the identification of numerous RBPs and miRNAs, there is an urgent need for new technologies to dissect the function of the cis-acting elements of RBPs and miRNAs. We describe post-transcriptional regulatory element sequencing (PTRE-seq), a massively parallel method for assaying the target sequences of miRNAs and RBPs. We use PTRE-seq to dissect sequence preferences and interactions between miRNAs and RBPs. The binding sites for these effector molecules influenced different aspects of the RNA lifecycle: RNA stability, translation efficiency, and translation initiation. In some cases, post-transcriptional control is modular, with different factors acting independently of each other, while in other cases factors show specific epistatic interactions. The throughput, flexibility, and reproducibility of PTRE-seq make it a valuable tool to study post-transcriptional regulation by 3'UTR elements.
[Mh] Termos MeSH primário: MicroRNAs/genética
Biossíntese de Proteínas
Processamento Pós-Transcricional do RNA
Proteínas de Ligação a RNA/genética
Elementos Reguladores de Transcrição
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Sequência de Bases
Sítios de Ligação
Linhagem Celular
Biblioteca Gênica
Células HEK293
Células HeLa
Seres Humanos
MicroRNAs/metabolismo
Ligação Proteica
Estabilidade de RNA
Proteínas de Ligação a RNA/metabolismo
Análise de Sequência de RNA
Termodinâmica
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (MicroRNAs); 0 (RNA-Binding Proteins); 0 (Transcription Factors); 0 (mirnlet7 microRNA, human); 0 (pumilio protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02745-0


  2 / 1982 MEDLINE  
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[PMID]:29305858
[Au] Autor:Kubota N; Yokoyama T; Hoshi N; Suyama M
[Ad] Endereço:Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
[Ti] Título:Identification of a candidate enhancer for DMRT3 involved in spastic cerebral palsy pathogenesis.
[So] Source:Biochem Biophys Res Commun;496(1):133-139, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cerebral palsy (CP) is a major neuronal disease and the most common movement disorder in children. Although environmental factors leading to CP have been greatly investigated, the genetic mechanism underlying CP is not well understood. Here we focused on two clinical reports that characterized a deletion involving the KANK1 gene locus in the 9p24.3 region. One report shows spastic CP and the other shows no spastic CP phenotype. Based on the epigenetic status and evolutionary conservation, we first found a functional genomic element at the noncoding region that was deleted only in patients with spastic CP. This element contains the retinoic acid receptor/retinoid X receptor (RAR/RXR) complex-binding motif that is widely conserved among placental mammals. RAR/RXR ChIP-seq data from mouse F9 embryonal carcinoma cells that were treated with trans-retinoic acids showed that the element has a binding ability. In addition, data regarding chromosome conformation capture from mouse neural progenitor and ES cells suggested that the element spatially interacts with the Doublesex and mab-3 related transcription factor 3 (Dmrt3) gene promoter that is located approximately 120 kb downstream of the RAR/RXR-binding site. Dmrt3 is detected in the developing mouse forebrain and in some interneurons in the spinal cord, and it works as a locomotion coordinator in horses and mice. Thus, the deletion of the cis-regulatory element for DMRT3 in humans may cause impaired development of the forebrain and gait abnormalities, resulting in spastic CP. In conclusion, this study provides new mechanistic insights into the genetic basis of CP.
[Mh] Termos MeSH primário: Paralisia Cerebral/genética
Mapeamento Cromossômico/métodos
Elementos Facilitadores Genéticos/genética
Predisposição Genética para Doença/genética
Genoma Humano/genética
Elementos Reguladores de Transcrição/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Sítios de Ligação
Seres Humanos
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DMRT1 protein); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


  3 / 1982 MEDLINE  
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[PMID]:29307818
[Au] Autor:Wei D; Feng L; Zhang W; Ma X; Cheng G; Li S; Wang L; Zhang S; Hong J; Guo H; Wang Y; Ning Y; Zan L
[Ad] Endereço:College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
[Ti] Título:Characterization of the promoter region of bovine SIX4: Roles of E-box and MyoD in the regulation of basal transcription.
[So] Source:Biochem Biophys Res Commun;496(1):44-50, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The sine oculis homeobox 4 (SIX4) gene belongs to the Six gene family and encodes an evolutionarily conserved transcription factor. Previous studies have demonstrated that SIX4 plays an essential role in proper muscle regeneration. However, the mechanisms regulating SIX4 transcription remain elusive. In the present study, we determined that bovine SIX4 was highly expressed in the longissimus thoracis and in undifferentiated Qinchuan cattle muscle cells (QCMCs) and that its protein localizes to both the cytoplasm and the nucleus. To elucidate the bovine the molecular mechanisms of SIX4 regulation, 1.3 kb of the 5'-regulatory region was obtained. MyoD and Ebox recognition sites were identified in the core promoter region at -522/-193 of the bovine SIX4 using a series of 5' deletion promoter plasmids in luciferase reporter assays. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with site-directed mutation and siRNA interference demonstrated that MyoD binding occurs at MyoD and Ebox recognition sites through direct and indirect mechanisms and play important roles in the transcriptional regulation of the bovine SIX4 promoter. Taken together, these interactions provide insight into the regulatory mechanisms of SIX4 transcription in mediating skeletal muscle growth in cattle.
[Mh] Termos MeSH primário: Bovinos/genética
Elementos E-Box/genética
Proteínas de Homeodomínio/genética
Proteína MyoD/genética
Regiões Promotoras Genéticas/genética
Elementos Reguladores de Transcrição/genética
Ativação Transcricional/genética
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica/genética
Transativadores/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Homeodomain Proteins); 0 (MyoD Protein); 0 (Trans-Activators)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  4 / 1982 MEDLINE  
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[PMID]:29045822
[Au] Autor:Fedoseeva DM; Kretova OV; Gorbacheva MA; Tchurikov NA
[Ad] Endereço:Engelhardt Institute of Molecular Biology, Moscow 119334, Russia.
[Ti] Título:Individual effects of the copia and gypsy enhancer and insulator on chromatin marks, eRNA synthesis, and binding of insulator proteins in transfected genetic constructs.
[So] Source:Gene;641:151-160, 2018 Jan 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Enhancers and insulators are involved in the regulation of gene expression, but the basic underlying mechanisms of action of these elements are unknown. We analyzed the individual effects of the enhancer and the insulator from Drosophila mobile elements copia [enh(copia)] and gypsy using transfected genetic constructs in S2 cells. This system excludes the influence of genomic cis regulatory elements. The enhancer-induced synthesis of 350-1050-nt-long enhancer RNAs (eRNAs) and H3K4me3 and H3K18ac marks, mainly in the region located about 300bp downstream of the enhancer. Insertion of the insulator between the enhancer and the promoter reduced these effects. We also observed the binding of dCTCF to the enhancer and to gypsy insulator. Our data indicate that a single gypsy insulator interacts with both the enhancer and the promoter, while two copies of the gypsy insulator preferentially interact with each other. Our results suggest the formation of chromatin loops that are shaped by the enhancer and the insulator.
[Mh] Termos MeSH primário: Cromatina/genética
Proteínas de Drosophila/genética
Drosophila/genética
Elementos Facilitadores Genéticos/genética
Marcadores Genéticos/genética
Elementos Isolantes/genética
Peptídeo Hidrolases/genética
RNA/genética
Retroelementos/genética
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Regulação da Expressão Gênica/genética
Regiões Promotoras Genéticas/genética
Elementos Reguladores de Transcrição/genética
Transfecção/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (Drosophila Proteins); 0 (Genetic Markers); 0 (Retroelements); 63231-63-0 (RNA); EC 3.4.- (Peptide Hydrolases); EC 3.4.23.- (Copia protein, Drosophila)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE


  5 / 1982 MEDLINE  
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[PMID]:28985361
[Au] Autor:Bonaldi K; Li Z; Kang SE; Breton G; Pruneda-Paz JL
[Ad] Endereço:Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
[Ti] Título:Novel cell surface luciferase reporter for high-throughput yeast one-hybrid screens.
[So] Source:Nucleic Acids Res;45(18):e157, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gene-centered yeast one-hybrid (Y1H) screens provide a powerful and effective strategy to identify transcription factor (TF)-promoter interactions. While genome-wide TF ORFeome clone collections are increasingly available, screening protocols have limitations inherent to the properties of the enzymatic reaction used to identify interactions and to the procedure required to perform the assay in a high-throughput format. Here, we present the development and validation of a streamlined strategy for quantitative and fully automated gene-centered Y1H screens using a novel cell surface Gaussia luciferase reporter.
[Mh] Termos MeSH primário: Genes Reporter
Ensaios de Triagem em Larga Escala/métodos
Luciferases/genética
Técnicas do Sistema de Duplo-Híbrido
[Mh] Termos MeSH secundário: Automação Laboratorial
Sítios de Ligação/genética
Regulação da Expressão Gênica/genética
Técnicas de Transferência de Genes
Organismos Geneticamente Modificados
Regiões Promotoras Genéticas
Ligação Proteica
Elementos Reguladores de Transcrição/genética
Saccharomyces cerevisiae
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Transcription Factors); EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx682


  6 / 1982 MEDLINE  
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[PMID]:28977652
[Au] Autor:Lavallée-Adam M; Cloutier P; Coulombe B; Blanchette M
[Ad] Endereço:McGill Centre for Bioinformatics and School of Computer Science, McGill University, Montréal, Québec H3A 0E9, Canada.
[Ti] Título:Functional 5' UTR motif discovery with LESMoN: Local Enrichment of Sequence Motifs in biological Networks.
[So] Source:Nucleic Acids Res;45(18):10415-10427, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Biological networks are rich representations of the relationships between entities such as genes or proteins and have become increasingly complete thanks to various high-throughput network mapping experimental approaches. Here, we propose a method to use such networks to guide the search for functional sequence motifs. Specifically, we introduce Local Enrichment of Sequence Motifs in biological Networks (LESMoN), an enumerative motif discovery algorithm that identifies 5' untranslated region (UTR) sequence motifs whose associated proteins form unexpectedly dense clusters in a given biological network. When applied to the human protein-protein interaction network from BioGRID, LESMoN identifies several highly significant 5' UTR sequence motifs, including both previously known motifs and uncharacterized ones. The vast majority of these motifs are evolutionary conserved and the genes containing them are significantly enriched for various gene ontology terms suggesting new associations between 5' UTR motifs and a number of biological processes. We validate in vivo the role in protein expression regulation of three motifs identified by LESMoN.
[Mh] Termos MeSH primário: Regiões 5´ não Traduzidas/genética
Algoritmos
Biologia Computacional/métodos
Regulação da Expressão Gênica
Redes Reguladoras de Genes
Elementos Reguladores de Transcrição
[Mh] Termos MeSH secundário: Sítios de Ligação/genética
Ontologia Genética
Estudos de Associação Genética
Seres Humanos
Mutação
Mapas de Interação de Proteínas/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Transcription Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx751


  7 / 1982 MEDLINE  
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[PMID]:28977594
[Au] Autor:Coons LA; Hewitt SC; Burkholder AB; McDonnell DP; Korach KS
[Ad] Endereço:Receptor Biology Section, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709.
[Ti] Título:DNA Sequence Constraints Define Functionally Active Steroid Nuclear Receptor Binding Sites in Chromatin.
[So] Source:Endocrinology;158(10):3212-3234, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gene regulatory programs are encoded in the sequence of the DNA. Since the completion of the Human Genome Project, millions of gene regulatory elements have been identified in the human genome. Understanding how each of those sites functionally contributes to gene regulation, however, remains a challenge for nearly every field of biology. Transcription factors influence cell function by interpreting information contained within cis-regulatory elements in chromatin. Whereas chromatin immunoprecipitation-sequencing has been used to identify and map transcription factor-DNA interactions, it has been difficult to assign functionality to the binding sites identified. Thus, in this study, we probed the transcriptional activity, DNA-binding competence, and functional activity of select nuclear receptor mutants in cellular and animal model systems and used this information to define the sequence constraints of functional steroid nuclear receptor cis-regulatory elements. Analysis of the architecture within sNR chromatin interacting sites revealed that only a small fraction of all sNR chromatin-interacting events is associated with transcriptional output and that this functionality is restricted to elements that vary from the consensus palindromic elements by one or two nucleotides. These findings define the transcriptional grammar necessary to predict functionality from regulatory sequences, with a multitude of future implications.
[Mh] Termos MeSH primário: Cromatina/química
DNA/química
Receptores Citoplasmáticos e Nucleares/fisiologia
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Sítios de Ligação/fisiologia
DNA/metabolismo
Receptor alfa de Estrogênio/genética
Feminino
Seres Humanos
Sequências Repetidas Invertidas/genética
Sequências Repetidas Invertidas/fisiologia
Camundongos
Mutação
Receptor Cross-Talk/fisiologia
Receptores Citoplasmáticos e Nucleares/genética
Receptores de Esteroides/genética
Receptores de Esteroides/fisiologia
Elementos Reguladores de Transcrição/genética
Sequências Reguladoras de Ácido Nucleico
Fatores de Transcrição/metabolismo
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (Estrogen Receptor alpha); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Receptors, Steroid); 0 (Transcription Factors); 9007-49-2 (DNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00468


  8 / 1982 MEDLINE  
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[PMID]:28977568
[Au] Autor:Hong S; Kim D
[Ad] Endereço:Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea.
[Ti] Título:Computational characterization of chromatin domain boundary-associated genomic elements.
[So] Source:Nucleic Acids Res;45(18):10403-10414, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Topologically associated domains (TADs) are 3D genomic structures with high internal interactions that play important roles in genome compaction and gene regulation. Their genomic locations and their association with CCCTC-binding factor (CTCF)-binding sites and transcription start sites (TSSs) were recently reported. However, the relationship between TADs and other genomic elements has not been systematically evaluated. This was addressed in the present study, with a focus on the enrichment of these genomic elements and their ability to predict the TAD boundary region. We found that consensus CTCF-binding sites were strongly associated with TAD boundaries as well as with the transcription factors (TFs) Zinc finger protein (ZNF)143 and Yin Yang (YY)1. TAD boundary-associated genomic elements include DNase I-hypersensitive sites, H3K36 trimethylation, TSSs, RNA polymerase II, and TFs such as Specificity protein 1, ZNF274 and SIX homeobox 5. Computational modeling with these genomic elements suggests that they have distinct roles in TAD boundary formation. We propose a structural model of TAD boundaries based on these findings that provides a basis for studying the mechanism of chromatin structure formation and gene regulation.
[Mh] Termos MeSH primário: Cromatina/genética
Mapeamento Cromossômico/métodos
Biologia Computacional/métodos
Genoma Humano
Elementos Reguladores de Transcrição
[Mh] Termos MeSH secundário: Algoritmos
Sítios de Ligação
Cromatina/metabolismo
Bases de Dados Genéticas
Regulação da Expressão Gênica
Componentes Genômicos
Seres Humanos
Regiões Promotoras Genéticas
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx738


  9 / 1982 MEDLINE  
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[PMID]:28973433
[Au] Autor:Stanulovic VS; Cauchy P; Assi SA; Hoogenkamp M
[Ad] Endereço:Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
[Ti] Título:LMO2 is required for TAL1 DNA binding activity and initiation of definitive haematopoiesis at the haemangioblast stage.
[So] Source:Nucleic Acids Res;45(17):9874-9888, 2017 Sep 29.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:LMO2 is a bridging factor within a DNA binding complex and is required for definitive haematopoiesis to occur. The developmental stage of the block in haematopoietic specification is not known. We show that Lmo2-/- mouse embryonic stem cells differentiated to Flk-1+ haemangioblasts, but less efficiently to haemogenic endothelium, which only produced primitive haematopoietic progenitors. Genome-wide approaches indicated that LMO2 is required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are important for the establishment of the haematopoietic developmental program. In the absence of LMO2, the target site recognition of TAL1 is impaired. The lack of LMO2 resulted in altered gene expression levels already at the haemangioblast stage, with transcription factor genes accounting for ∼15% of affected genes. Comparison of Lmo2-/- with Tal1-/- Flk-1+ cells further showed that TAL1 was required to initiate or sustain Lmo2 expression.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/genética
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Proteínas de Ligação a DNA/genética
DNA/genética
Genoma
Hemangioblastos/metabolismo
Proteínas com Domínio LIM/genética
Células-Tronco Embrionárias Murinas/metabolismo
Proteínas Proto-Oncogênicas/genética
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/deficiência
Animais
Sequência de Bases
Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência
Diferenciação Celular
Linhagem Celular
DNA/metabolismo
Proteínas de Ligação a DNA/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Hemangioblastos/citologia
Hematopoese/genética
Proteínas com Domínio LIM/deficiência
Proteínas com Domínio LIM/metabolismo
Camundongos
Células-Tronco Embrionárias Murinas/citologia
Ligação Proteica
Proteínas Proto-Oncogênicas/deficiência
Elementos Reguladores de Transcrição
Transdução de Sinais
Proteína 1 de Leucemia Linfocítica Aguda de Células T
Transcrição Genética
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/deficiência
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (DNA-Binding Proteins); 0 (LIM Domain Proteins); 0 (Ldb1 protein, mouse); 0 (Lmo2 protein, mouse); 0 (Proto-Oncogene Proteins); 0 (T-Cell Acute Lymphocytic Leukemia Protein 1); 0 (Tal1 protein, mouse); 9007-49-2 (DNA); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx573


  10 / 1982 MEDLINE  
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[PMID]:28916711
[Au] Autor:Huang P; Keller CA; Giardine B; Grevet JD; Davies JOJ; Hughes JR; Kurita R; Nakamura Y; Hardison RC; Blobel GA
[Ad] Endereço:Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
[Ti] Título:Comparative analysis of three-dimensional chromosomal architecture identifies a novel fetal hemoglobin regulatory element.
[So] Source:Genes Dev;31(16):1704-1713, 2017 Aug 15.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromatin structure is tightly intertwined with transcription regulation. Here we compared the chromosomal architectures of fetal and adult human erythroblasts and found that, globally, chromatin structures and compartments A/B are highly similar at both developmental stages. At a finer scale, we detected distinct folding patterns at the developmentally controlled ß-globin locus. Specifically, new fetal stage-specific contacts were uncovered between a region separating the fetal (γ) and adult (δ and ß) globin genes (encompassing the and noncoding genes) and two distal chromosomal sites (HS5 and 3'HS1) that flank the locus. In contrast, in adult cells, the - region contacts the embryonic ε-globin gene, physically separating the fetal globin genes from the enhancer (locus control region [LCR]). Deletion of the region in adult cells alters contact landscapes in ways more closely resembling those of fetal cells, including increased LCR-γ-globin contacts. These changes are accompanied by strong increases in γ-globin transcription. Notably, the effects of removal on chromatin architecture and gene expression closely mimic those of deleting the fetal globin repressor BCL11A, implicating BCL11A in the function of the region. Our results uncover a new critical regulatory region as a potential target for therapeutic genome editing for hemoglobinopathies and highlight the power of chromosome conformation analysis in discovering new control elements.
[Mh] Termos MeSH primário: Cromatina/química
Eritroblastos/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Elementos Reguladores de Transcrição
Globinas beta/genética
[Mh] Termos MeSH secundário: Adulto
Proteínas de Transporte/genética
Feto
Inativação Gênica
Seres Humanos
Região de Controle de Locus Gênico
Proteínas Nucleares/genética
Pseudogenes
Transcriptoma
gama-Globinas/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BCL11A protein, human); 0 (Carrier Proteins); 0 (Chromatin); 0 (Nuclear Proteins); 0 (beta-Globins); 0 (gamma-Globins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE
[do] DOI:10.1101/gad.303461.117



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