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1.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800945

RESUMO

A combined Genotyping By Sequencing (GBS) and methylated DNA immunoprecipitation (MeDIP) protocol was used to identify-in parallel-genetic variation (Genomic-Wide Association Studies (GWAS) and epigenetic differences of Differentially Methylated Regions (DMR) in the genome of spermatozoa from the porcine animal model. Breeding boars with good semen quality (n = 11) and specific and well-documented differences in fertility (farrowing rate, FR) and prolificacy (litter size, LS) (n = 7) in artificial insemination programs, using combined FR and LS, were categorized as High Fertile (HF, n = 4) or Low Fertile (LF, n = 3), and boars with Unknown Fertility (UF, n = 4) were tested for eventual epigenetical similarity with those fertility-proven. We identified 165,944 Single Nucleotide Polymorphisms (SNPs) that explained 14-15% of variance among selection lines. Between HF and LF individuals (n = 7, 4 HF and 3 LF), we identified 169 SNPs with p ≤ 0.00015, which explained 58% of the variance. For the epigenetic analyses, we considered fertility and period of ejaculate collection (late-summer and mid-autumn). Approximately three times more DMRs were observed in HF than in LF boars across these periods. Interestingly, UF boars were clearly clustered with one of the other HF or LF groups. The highest differences in DMRs between HF and LF experimental groups across the pig genome were located in the chr 3, 9, 13, and 16, with most DMRs being hypermethylated in LF boars. In both HF and LF boars, DMRs were mostly hypermethylated in late-summer compared to mid-autumn. Three overlaps were detected between SNPs (p ≤ 0.0005, n = 1318) and CpG sites within DMRs. In conclusion, fertility levels in breeding males including FR and LS can be discerned using methylome analyses. The findings in this biomedical animal model ought to be applied besides sire selection for andrological diagnosis of idiopathic sub/infertility.


Assuntos
Metilação de DNA , Fertilidade/genética , Infertilidade Masculina/genética , Análise do Sêmen/métodos , Espermatozoides/química , Animais , Sequência de Bases , Cromossomos/genética , Biblioteca Gênica , Ontologia Genética , Estudo de Associação Genômica Ampla , Humanos , Infertilidade Masculina/veterinária , Inseminação Artificial/veterinária , Masculino , Modelos Animais , Polimorfismo de Nucleotídeo Único , Estações do Ano , Alinhamento de Sequência , Manejo de Espécimes , Suínos
2.
BMC Bioinformatics ; 22(Suppl 2): 43, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902433

RESUMO

BACKGROUND: High-throughput sequencing Chromosome Conformation Capture (Hi-C) allows the study of DNA interactions and 3D chromosome folding at the genome-wide scale. Usually, these data are represented as matrices describing the binary contacts among the different chromosome regions. On the other hand, a graph-based representation can be advantageous to describe the complex topology achieved by the DNA in the nucleus of eukaryotic cells. METHODS: Here we discuss the use of a graph database for storing and analysing data achieved by performing Hi-C experiments. The main issue is the size of the produced data and, working with a graph-based representation, the consequent necessity of adequately managing a large number of edges (contacts) connecting nodes (genes), which represents the sources of information. For this, currently available graph visualisation tools and libraries fall short with Hi-C data. The use of graph databases, instead, supports both the analysis and the visualisation of the spatial pattern present in Hi-C data, in particular for comparing different experiments or for re-mapping omics data in a space-aware context efficiently. In particular, the possibility of describing graphs through statistical indicators and, even more, the capability of correlating them through statistical distributions allows highlighting similarities and differences among different Hi-C experiments, in different cell conditions or different cell types. RESULTS: These concepts have been implemented in NeoHiC, an open-source and user-friendly web application for the progressive visualisation and analysis of Hi-C networks based on the use of the Neo4j graph database (version 3.5). CONCLUSION: With the accumulation of more experiments, the tool will provide invaluable support to compare neighbours of genes across experiments and conditions, helping in highlighting changes in functional domains and identifying new co-organised genomic compartments.


Assuntos
Cromatina , Cromossomos , Cromatina/genética , Genoma , Genômica , Conformação Molecular
3.
BMC Bioinformatics ; 22(1): 183, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33838653

RESUMO

BACKGROUND: The nucleus of eukaryotic cells spatially packages chromosomes into a hierarchical and distinct segregation that plays critical roles in maintaining transcription regulation. High-throughput methods of chromosome conformation capture, such as Hi-C, have revealed topologically associating domains (TADs) that are defined by biased chromatin interactions within them. RESULTS: We introduce a novel method, HiCKey, to decipher hierarchical TAD structures in Hi-C data and compare them across samples. We first derive a generalized likelihood-ratio (GLR) test for detecting change-points in an interaction matrix that follows a negative binomial distribution or general mixture distribution. We then employ several optimal search strategies to decipher hierarchical TADs with p values calculated by the GLR test. Large-scale validations of simulation data show that HiCKey has good precision in recalling known TADs and is robust against random collisions of chromatin interactions. By applying HiCKey to Hi-C data of seven human cell lines, we identified multiple layers of TAD organization among them, but the vast majority had no more than four layers. In particular, we found that TAD boundaries are significantly enriched in active chromosomal regions compared to repressed regions. CONCLUSIONS: HiCKey is optimized for processing large matrices constructed from high-resolution Hi-C experiments. The method and theoretical result of the GLR test provide a general framework for significance testing of similar experimental chromatin interaction data that may not fully follow negative binomial distributions but rather more general mixture distributions.


Assuntos
Cromatina , Cromossomos , Núcleo Celular , Cromatina/genética , Simulação por Computador , Regulação da Expressão Gênica , Humanos
4.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(1): 122-130, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33899436

RESUMO

Human chromosomes karyotyping is an important means to diagnose genetic diseases. Chromosome image type recognition is a key step in the karyotyping process. Accurate and efficient identification is of great significance for automatic chromosome karyotyping. In this paper, we propose a model named segmentally recalibrated dense convolutional network (SR-DenseNet). In each stage of the model, the dense connected network layers is used to extract the features of different abstract levels of chromosomes automatically, and then the concatenation of all the layers which extract different local features is recalibrated with squeeze-and-excitation (SE) block. SE blocks explicitly construct learnable structures for importance of the features. Then a model fusion method is proposed and an expert group of chromosome recognition models is constructed. On the public available Copenhagen chromosome recognition dataset (G-bands) the proposed model achieves error rate of only 1.60%, and with model fusion the error further drops to 0.99%. On the Padova chromosome dataset (Q-bands) the model gets the corresponding error rate of 6.67%, and with model fusion the error further drops to 5.98%. The experimental results show that the method proposed in this paper is effective and has the potential to realize the automation of chromosome type recognition.


Assuntos
Cromossomos , Redes Neurais de Computação , Humanos
5.
Nat Commun ; 12(1): 1485, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674578

RESUMO

Yeast whole genome sequencing (WGS) lacks end-to-end workflows that identify genetic engineering. Here we present Prymetime, a tool that assembles yeast plasmids and chromosomes and annotates genetic engineering sequences. It is a hybrid workflow-it uses short and long reads as inputs to perform separate linear and circular assembly steps. This structure is necessary to accurately resolve genetic engineering sequences in plasmids and the genome. We show this by assembling diverse engineered yeasts, in some cases revealing unintended deletions and integrations. Furthermore, the resulting whole genomes are high quality, although the underlying assembly software does not consistently resolve highly repetitive genome features. Finally, we assemble plasmids and genome integrations from metagenomic sequencing, even with 1 engineered cell in 1000. This work is a blueprint for building WGS workflows and establishes WGS-based identification of yeast genetic engineering.


Assuntos
Engenharia Genética/métodos , Genoma Fúngico , Saccharomyces cerevisiae/genética , Sequenciamento Completo do Genoma/métodos , Sequência de Bases , Cromossomos , Cromossomos Artificiais de Levedura , Clonagem Molecular , Simulação por Computador , Mapeamento de Sequências Contíguas/métodos , Metagenoma , Metagenômica , Plasmídeos , Software , Transformação Genética
6.
Mol Cell ; 81(8): 1601-1616, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33770487

RESUMO

The influence of genome organization on transcription is central to our understanding of cell type specification. Higher-order genome organization is established through short- and long-range DNA interactions. Coordination of these interactions, from single atoms to entire chromosomes, plays a fundamental role in transcriptional control of gene expression. Loss of this coupling can result in disease. Analysis of transcriptional regulation typically involves disparate experimental approaches, from structural studies that define angstrom-level interactions to cell-biological and genomic approaches that assess mesoscale relationships. Thus, to fully understand the mechanisms that regulate gene expression, it is critical to integrate the findings gained across these distinct size scales. In this review, I illustrate fundamental ways in which cells regulate transcription in the context of genome organization.


Assuntos
Pareamento de Bases/genética , Cromossomos/genética , Transcrição Genética/genética , Animais , Regulação da Expressão Gênica/genética , Humanos , Elementos Reguladores de Transcrição/genética
7.
Biol Lett ; 17(3): 20200915, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33653095

RESUMO

Intralocus sexual conflict arises when the expression of shared alleles at a single locus generates opposite fitness effects in each sex (i.e. sexually antagonistic alleles), preventing each sex from reaching its sex-specific optimum. Despite its importance to reproductive success, the relative contribution of intralocus sexual conflict to male pre- and post-copulatory success is not well-understood. Here, we used a female-limited X-chromosome (FLX) evolution experiment in Drosophila melanogaster to limit the inheritance of the X-chromosome to the matriline, eliminating possible counter-selection in males and allowing the X-chromosome to accumulate female-benefit alleles. After more than 100 generations of FLX evolution, we studied the effect of the evolved X-chromosome on male attractiveness and sperm competitiveness. We found a non-significant increase in attractiveness and decrease in sperm offence ability in males expressing the evolved X-chromosomes, but a significant increase in their ability to avoid displacement by other males' sperm. This is consistent with a trade-off between these traits, perhaps mediated by differences in body size, causing a small net reduction in overall male fitness in the FLX lines. These results indicate that the X-chromosome in D. melanogaster is subject to selection via intralocus sexual conflict in males.


Assuntos
Drosophila melanogaster , Caracteres Sexuais , Animais , Evolução Biológica , Tamanho Corporal , Cromossomos , Drosophila melanogaster/genética , Feminino , Masculino , Reprodução , Seleção Genética , Comportamento Sexual Animal
8.
Zool Res ; 42(3): 262-266, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33764016

RESUMO

The Dianchi golden-line barbel, Sinocyclocheilus grahami (Regan, 1904), is one of the "Four Famous Fishes" of Yunnan Province, China. Given its economic value, this species has been artificially bred successfully since 2007, with a nationally selected breed (" S. grahami, Bayou No. 1") certified in 2018. For the future utilization of this species, its growth rate, disease resistance, and wild adaptability need to be improved, which could be achieved with the help of molecular marker-assisted selection (MAS). In the current study, we constructed the first chromosome-level genome of S. grahami, assembled 48 pseudo-chromosomes, and obtained a genome assembly of 1.49 Gb. We also performed QTL-seq analysis of S. grahami using the highest and lowest bulks (i.e., largest and smallest size) in both a sibling and random population. We screened two quantitative trait loci (QTLs) (Chr3, 14.9-39.1 Mb and Chr17, 4.1-27.4 Mb) as the major growth-related locations. Several candidate genes (e.g., map2k5, stat1, phf21a, sox6, and smad6) were also identified, with functions related to growth, such as cell differentiation, neuronal development, skeletal muscle development, chondrogenesis, and immunity. These results built a solid foundation for in-depth MAS studies on the growth traits of S. grahami.


Assuntos
Cyprinidae/crescimento & desenvolvimento , Cyprinidae/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Genoma , Locos de Características Quantitativas/genética , Animais , Cromossomos , Ligação Genética , Estudo de Associação Genômica Ampla
9.
J Vis Exp ; (169)2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749670

RESUMO

The genome is associated with several structures inside cell nuclei, in order to regulate its activity and anchor it in specific locations. These structures are collectively known as the nucleoskeleton and include the nuclear lamina, the nucleoli, and nuclear bodies. Although many variants of fluorescence in situ hybridization (FISH) exist to study the genome and its organization, these are often limited by resolution and provide insufficient information on the genome's association with nuclear structures. The DNA halo method uses high salt concentrations and nonionic detergents to generate DNA loops that remain anchored to structures within nuclei through attachment regions within the genome. Here, soluble nuclear proteins, such as histones, lipids, and DNA not tightly bound to the nuclear matrix, are extracted. This leads to the formation of a halo of unattached DNA surrounding a residual nucleus which itself contains DNA closely associated with internal nuclear structures and extraction-resistant proteins. These extended DNA strands enable increased resolution and can facilitate physical mapping. In combination with FISH, this method has the added advantage of studying genomic interactions with all the structures that the genome is anchored by. This technique, termed HALO-FISH, is highly versatile whereby DNA halos can be coupled with nucleic acid probes to reveal gene loci, whole chromosomes, alpha satellite, telomeres and even RNA. This technique provides an insight into nuclear organization and function in normal cells and in disease progression such as with cancer.


Assuntos
Cromossomos/metabolismo , DNA/metabolismo , Loci Gênicos , Hibridização in Situ Fluorescente , Telômero/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Cromossomos Artificiais Bacterianos/metabolismo , Derme/citologia , Fibroblastos/metabolismo , Humanos , Processamento de Imagem Assistida por Computador
10.
Mol Cell ; 81(6): 1128-1129, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33740472

RESUMO

Huang et al. (2021) identified a mechanism acting through the arginine methyltransferase PRMT6 that stabilizes the interaction of RCC1 with chromatin, promoting cell proliferation and tumorigenicity. Targeting this mechanism might enhance the treatment of tumors such as glioblastoma.


Assuntos
Glioblastoma , Proteínas Nucleares , Carcinogênese/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Cromossomos/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Metilação , Mitose , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Células-Tronco/metabolismo
11.
Mol Cell ; 81(5): 901-904, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667381

RESUMO

Combining live-cell imaging, cytogenetics, genome sequencing, and in vitro evolution, Shoshani et al. (2020) revealed deep connections between chromothripsis, the catastrophic shattering of a chromosome in abnormal nuclear structures, and gene amplification, a frequent culprit of oncogenic activation.


Assuntos
Cromotripsia , Neoplasias , Cromossomos/genética , Análise Citogenética , Amplificação de Genes , Humanos , Neoplasias/genética
12.
Nat Rev Mol Cell Biol ; 22(4): 283-298, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33564154

RESUMO

The regulation of telomere length in mammals is crucial for chromosome end-capping and thus for maintaining genome stability and cellular lifespan. This process requires coordination between telomeric protein complexes and the ribonucleoprotein telomerase, which extends the telomeric DNA. Telomeric proteins modulate telomere architecture, recruit telomerase to accessible telomeres and orchestrate the conversion of the newly synthesized telomeric single-stranded DNA tail into double-stranded DNA. Dysfunctional telomere maintenance leads to telomere shortening, which causes human diseases including bone marrow failure, premature ageing and cancer. Recent studies provide new insights into telomerase-related interactions (the 'telomere replisome') and reveal new challenges for future telomere structural biology endeavours owing to the dynamic nature of telomere architecture and the great number of structures that telomeres form. In this Review, we discuss recently determined structures of the shelterin and CTC1-STN1-TEN1 (CST) complexes, how they may participate in the regulation of telomere replication and chromosome end-capping, and how disease-causing mutations in their encoding genes may affect specific functions. Major outstanding questions in the field include how all of the telomere components assemble relative to each other and how the switching between different telomere structures is achieved.


Assuntos
Cromatina/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/metabolismo , Animais , Cromossomos/metabolismo , DNA/metabolismo , Humanos , Telomerase/metabolismo
13.
Nat Protoc ; 16(3): 1647-1713, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33619390

RESUMO

Chromatin conformation capture (3C) methods and fluorescent in situ hybridization (FISH) microscopy have been used to investigate the spatial organization of the genome. Although powerful, both techniques have limitations. Hi-C is challenging for low cell numbers and requires very deep sequencing to achieve its high resolution. In contrast, FISH can be done on small cell numbers and capture rare cell populations, but typically targets pairs of loci at a lower resolution. Here we detail a protocol for optical reconstruction of chromatin architecture (ORCA), a microscopy approach to trace the 3D DNA path within the nuclei of fixed tissues and cultured cells with a genomic resolution as fine as 2 kb and a throughput of ~10,000 cells per experiment. ORCA can identify structural features with comparable resolution to Hi-C while providing single-cell resolution and multimodal measurements characteristic of microscopy. We describe how to use this DNA labeling in parallel with multiplexed labeling of dozens of RNAs to relate chromatin structure and gene expression in the same cells. Oligopaint probe design, primary probe making, sample collection, cryosectioning and RNA/DNA primary probe hybridization can be completed in 1.5 weeks, while automated RNA/DNA barcode hybridization and RNA/DNA imaging typically takes 2-6 d for data collection and 2-7 d for the automated steps of image analysis.


Assuntos
Hibridização in Situ Fluorescente/métodos , Microscopia de Fluorescência/métodos , Mapeamento por Restrição Óptica/métodos , Linhagem Celular , Núcleo Celular/genética , Células Cultivadas , Cromatina/metabolismo , Imunoprecipitação da Cromatina/métodos , Cromossomos/genética , DNA/química , DNA/genética , Sondas de DNA , Corantes Fluorescentes/química , Técnicas Genéticas , Genoma/genética , Genômica/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , RNA/química , RNA/genética
14.
Nat Commun ; 12(1): 1344, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637722

RESUMO

During cellular differentiation chromosome conformation is intricately remodelled to support the lineage-specific transcriptional programs required for initiating and maintaining lineage identity. When these changes occur in relation to cell cycle, division and time in response to cellular activation and differentiation signals has yet to be explored, although it has been proposed to occur during DNA synthesis or after mitosis. Here, we elucidate the chromosome conformational changes in B lymphocytes as they differentiate and expand from a naive, quiescent state into antibody secreting plasma cells. We find gene-regulatory chromosome reorganization in late G1 phase before the first division, and that this configuration is remarkably stable as the cells massively and rapidly clonally expand. A second wave of conformational change occurs as cells terminally differentiate into plasma cells, coincident with increased time in G1 phase. These results provide further explanation for how lymphocyte fate is imprinted prior to the first division. They also suggest that chromosome reconfiguration occurs prior to DNA replication and mitosis, and is linked to a gene expression program that controls the differentiation process required for the generation of immunity.


Assuntos
Linfócitos B/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Genoma , Ativação Linfocitária/genética , Ativação Linfocitária/fisiologia , Animais , Células Produtoras de Anticorpos , Ciclo Celular , Divisão Celular , Cromatina , Cromossomos , Replicação do DNA , Epigenômica , Fase G1/genética , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitose , Plasmócitos
15.
DNA Cell Biol ; 40(2): 293-302, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33605798

RESUMO

Olfaction is a complicated process that begins with the specific binding of volatile odorant molecules to dedicated olfactory receptors (ORs) in the olfactory epithelium and plays a pivotal role in the survival of mammals. The OR subgenome of the snow leopard has remained largely unexplored, and thus, investigation of the OR system would shed light on the evolutionary dynamics of the snow leopard OR repertoires and genetic evidence for environmental adaptation. In this study, we conducted genome-wide identification and characterization of OR genes in the snow leopard and compared them to all other Panthera species. A total of 213, 294, 624, 305, and 253 functional OR genes were identified in the snow leopard, lion, jaguar, leopard, and tiger, respectively. The phylogenetic relationships of functional Panthera OR genes were illustrated, which comprised 69 families and 350 subfamilies distributed in two classes (Class I and Class II). Comparative analysis of the five Panthera species indicated 115 shared and 5 snow leopard-specific clusters. The potential odorant specificity of certain snow leopard OR genes was identified by similarities to human protein sequences and we identified odorants such as eugenol methyl ether that had the most OR genes. Since our references for odorants were from human studies, possible odorants from snow leopard-specific OR genes need further investigation. The lowest number of OR genes for the snow leopard among Panthera species possibly revealed the association between OR gene family contraction and high-altitude adaptation, which needed further and deeper investigation. This systematic study of OR genes in the snow leopard will provide a solid foundation for further study of olfactory function and variation in the snow leopard.


Assuntos
Cromossomos/genética , Espécies em Perigo de Extinção , Genômica , Panthera , Receptores Odorantes/genética , Sequência de Aminoácidos , Animais , Filogenia , Receptores Odorantes/química
16.
Methods Mol Biol ; 2218: 137-155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606229

RESUMO

Oocyte production is crucial for sexual reproduction. Recent findings in zebrafish and other established model organisms emphasize that the early steps of oogenesis involve the coordination of simultaneous and tightly sequential processes across cellular compartments and between sister cells. To fully understand the mechanistic framework of these coordinated processes, cellular and morphological analysis in high temporal resolution is required. Here, we provide a protocol for four-dimensional live time-lapse analysis of cultured juvenile zebrafish ovaries. We describe how multiple-stage oocytes can be simultaneously analyzed in single ovaries, and several ovaries can be processed in single experiments. In addition, we detail adequate conditions for quantitative image acquisition. Finally, we demonstrate that using this protocol, we successfully capture rapid meiotic chromosomal movements in early prophase for the first time in zebrafish oocytes, in four dimensions and in vivo. Our protocol expands the use of the zebrafish as a model system to understand germ cell and ovarian development in postembryonic stages.


Assuntos
Cromossomos/fisiologia , Meiose/fisiologia , Oogênese/fisiologia , Ovário/fisiologia , Imagem com Lapso de Tempo/métodos , Peixe-Zebra/fisiologia , Animais , Feminino , Oócitos , Diferenciação Sexual/fisiologia
17.
Sci Data ; 8(1): 60, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574331

RESUMO

Caligus rogercresseyi, commonly known as sea louse, is an ectoparasite copepod that impacts the salmon aquaculture in Chile, causing losses of hundreds of million dollars per year. In this study, we report a chromosome-scale assembly of the sea louse (C. rogercresseyi) genome based on single-molecule real-time sequencing (SMRT) and proximity ligation (Hi-C) analysis. Coding RNAs and non-coding RNAs, and specifically long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were identified through whole transcriptome sequencing from different life stages. A total of 23,686 protein-coding genes and 12,558 non-coding RNAs were annotated. In addition, 6,308 lncRNAs and 5,774 miRNAs were found to be transcriptionally active from larvae to adult stages. Taken together, this genomic resource for C. rogercresseyi represents a valuable tool to develop sustainable control strategies in the salmon aquaculture industry.


Assuntos
Copépodes/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Transcriptoma , Animais , Cromossomos , Copépodes/patogenicidade , Doenças dos Peixes/parasitologia , Estágios do Ciclo de Vida/genética , Salmão/parasitologia
18.
Nature ; 590(7847): 554-555, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33597775
19.
Nat Commun ; 12(1): 1011, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579945

RESUMO

Vertebrate genomes are partitioned into contact domains defined by enhanced internal contact frequency and formed by two principal mechanisms: compartmentalization of transcriptionally active and inactive domains, and stalling of chromosomal loop-extruding cohesin by CTCF bound at domain boundaries. While Drosophila has widespread contact domains and CTCF, it is currently unclear whether CTCF-dependent domains exist in flies. We genetically ablate CTCF in Drosophila and examine impacts on genome folding and transcriptional regulation in the central nervous system. We find that CTCF is required to form a small fraction of all domain boundaries, while critically controlling expression patterns of certain genes and supporting nervous system function. We also find that CTCF recruits the pervasive boundary-associated factor Cp190 to CTCF-occupied boundaries and co-regulates a subset of genes near boundaries together with Cp190. These results highlight a profound difference in CTCF-requirement for genome folding in flies and vertebrates, in which a large fraction of boundaries are CTCF-dependent and suggest that CTCF has played mutable roles in genome architecture and direct gene expression control during metazoan evolution.


Assuntos
Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Drosophila/genética , Genoma , Animais , Cromatina , Cromossomos/metabolismo , Biologia do Desenvolvimento , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Técnicas de Inativação de Genes , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo
20.
PLoS Pathog ; 17(2): e1009207, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33539484

RESUMO

The recent Coronavirus Disease 2019 pandemic has once again reminded us the importance of understanding infectious diseases. One important but understudied area in infectious disease research is the role of nuclear architecture or the physical arrangement of the genome in the nucleus in controlling gene regulation and pathogenicity. Recent advances in research methods, such as Genome-wide chromosome conformation capture using high-throughput sequencing (Hi-C), have allowed for easier analysis of nuclear architecture and chromosomal reorganization in both the infectious disease agents themselves as well as in their host cells. This review will discuss broadly on what is known about nuclear architecture in infectious disease, with an emphasis on chromosomal reorganization, and briefly discuss what steps are required next in the field.


Assuntos
Núcleo Celular/genética , Cromatina/metabolismo , Doenças Transmissíveis/genética , Animais , /metabolismo , Núcleo Celular/metabolismo , Cromatina/genética , Cromossomos/genética , Cromossomos/metabolismo , Doenças Transmissíveis/metabolismo , Regulação da Expressão Gênica , Humanos
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