Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Language
Year
  • 1
    Language: English
    In: Nature, November 2018, Vol.563(7729), pp.121-125
    Description: Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses-Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing-that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation.
    Keywords: Antigenic Variation -- Genetics ; Chromatin -- Genetics ; DNA, Protozoan -- Metabolism ; Genome -- Genetics ; Trypanosoma Brucei Brucei -- Genetics
    ISSN: 00280836
    E-ISSN: 1476-4687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Nature Biotechnology, 2013, Vol.31(12), p.1143
    Description: Despite advances in DNA sequencing technology, assembly of complex genomes remains a major challenge, particularly for genomes sequenced using short reads, which yield highly fragmented assemblies. Here we show that genome-wide in vivo chromatin interaction frequency data, which are measurable with chromosome conformation capture-based experiments, can be used as genomic distance proxies to accurately position individual contigs without requiring any sequence overlap. We also use these data to construct approximate genome scaffolds de novo. Applying our approach to incomplete regions of the human genome, we predict the positions of 65 previously unplaced contigs, in agreement with alternative methods in 26/31 cases attempted in common. Our approach can theoretically bridge any gap size and should be applicable to any species for which global chromatin interaction data can be generated.
    Keywords: Medicine ; Engineering ; Biology;
    ISSN: 1087-0156
    E-ISSN: 15461696
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Nature, 28 July 2016, Vol.535(7613), pp.575-9
    Description: X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD-like structures after XCI. These findings suggest a key role for transcription and CTCF in the formation of TADs in the context of the Xi chromosome in neural progenitors.
    Keywords: X Chromosome Inactivation ; Chromosomes, Mammalian -- Metabolism ; X Chromosome -- Metabolism
    ISSN: 00280836
    E-ISSN: 1476-4687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Nature, 2016
    ISSN: 0028-0836
    Source: Nature Publishing Group
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Journal of Molecular Biology, 2007, Vol.369(2), pp.553-566
    Description: Most animal toxins are short proteins that appear in venom and vary in sequence, structure and function. A common characteristic of many such toxins is their apparent structural stability. Sporadic instances of endogenous toxin-like proteins that function in non-venom context have been reported. We have utilized machine learning methodology, based on sequence-derived features and guided by the notion of structural stability, in order to conduct a large-scale search for toxin and toxin-like proteins. Application of the method to insect and mammalian sequences revealed novel families of toxin-like proteins. One of these proteins shows significant similarity to ion channel inhibitors that are expressed in cone snail and assassin bug venom, and is surprisingly expressed in the bee brain. A toxicity assay in which the protein was injected to fish induced a strong yet reversible paralytic effect. We suggest that the protein may function as an endogenous modulator of voltage-gated Ca channels. Additionally, we have identified a novel mammalian cluster of toxin-like proteins that are expressed in the testis. We suggest that these proteins might be involved in regulation of nicotinic acetylcholine receptors that affect the acrosome reaction and sperm motility. Finally, we highlight a possible evolutionary link between venom toxins and antibacterial proteins. We expect our methodology to enhance the discovery of additional novel protein families.
    Keywords: Anlp ; Oclp ; Short Proteins ; Genome Annotation ; Raalin ; Biology ; Chemistry
    ISSN: 0022-2836
    E-ISSN: 1089-8638
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Nature, 2008, Vol.458(7236), p.362
    Description: Nucleosome organization is critical for gene regulation (1). In living cells this organization is determined by multiple factors, including the action of chromatin remodellers (2), competition with site-specific DNA-binding proteins (3), and the DNA sequence preferences of the nucleosomes themselves (4-8). However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo (7,9-11), because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for ~40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.
    Keywords: Nucleosomes -- Structure ; Eukaryotes -- Genetic Aspects ; Dna Sequencing -- Usage ; Base Sequence -- Properties;
    ISSN: 0028-0836
    E-ISSN: 14764687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: PLoS ONE, 2010, Vol.5(2), p.e9129
    Description: Active eukaryotic regulatory sites are characterized by open chromatin, and yeast promoters and transcription factor binding sites (TFBSs) typically have low intrinsic nucleosome occupancy. Here, we show that in contrast to yeast, DNA at human promoters, enhancers, and TFBSs generally encodes high intrinsic nucleosome occupancy. In most cases we examined, these elements also have high experimentally measured nucleosome occupancy in vivo . These regions typically have high G+C content, which correlates positively with intrinsic nucleosome occupancy, and are depleted for nucleosome-excluding poly-A sequences. We propose that high nucleosome preference is directly encoded at regulatory sequences in the human genome to restrict access to regulatory information that will ultimately be utilized in only a subset of differentiated cells.
    Keywords: Research Article ; Computational Biology -- Genomics ; Computational Biology -- Transcriptional Regulation ; Molecular Biology -- Bioinformatics ; Molecular Biology -- Chromatin Structure
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Nature Structural & Molecular Biology, 2010, Vol.17(8), p.918
    Description: Nucleosomes occlude their wrapped DNA, strongly influencing the accessibility of functional DNA binding sites. This has led to interest in genome-wide mapping of nucleosome positions and in understanding the principles that govern these positions. We recently compared the positions of nucleosomes reconstituted in vitro to a map of in vivo nucleosome locations. We found high similarity between the maps, implying that intrinsic DNA sequence preferences of nucleosomes have a major role in determining the organization of nucleosomes in vivo.
    Keywords: Animals–Genetics ; Base Sequence–Metabolism ; Genome, Fungal–Genetics ; Histones–Metabolism ; Humans–Genetics ; Nucleosomes–Metabolism ; Nucleosomes–Metabolism ; Protein Binding–Metabolism ; Saccharomyces Cerevisiae–Metabolism ; Saccharomyces Cerevisiae–Metabolism ; Molecular Biology ; Genomics ; Comparative Studies ; Deoxyribonucleic Acid–DNA ; Binding Sites ; Histones ; Nucleosomes;
    ISSN: 1545-9993
    E-ISSN: 15459985
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Description: Processed Hi-C interaction matrices, saved in numpy npz format. Matrices were processed using Dekker lab cMapping pipeline. Raw sequence data was taken from: Hap1: Haarhuis et al 10.1016/j.cell.2017.04.013 IMR90, H1ESC, MESC, MCORTEX: Dixon et al 10.1038/nature11082 Worm: Crane et al 10.1038/nature14450 Caulobacter: Le et al 10.1126/science.1242059  ...
    Keywords: Hi-C
    Source: DataCite
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Description: Processed Hi-C interaction matrices, saved in numpy npz format. Matrices were processed using Dekker lab cMapping pipeline. Raw sequence data was taken from: Hap1: Haarhuis et al 10.1016/j.cell.2017.04.013 IMR90, H1ESC, MESC, MCORTEX: Dixon et al 10.1038/nature11082 Worm: Crane et al 10.1038/nature14450 Caulobacter: Le et al 10.1126/science.1242059  ...
    Keywords: Hi-C
    Source: DataCite
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages