Tandem repeats (periodicities) constitute a significant part of the genomes of various organisms. They are often used as molecular markers in problems of differentiation of related objects. As such, ...bacteria of pseudotuberculosis and plague are considered. Genetically, the pathogen causing plague, Yersinia pestis, is very similar to Yersinia pseudotuberculosis. A comparison is made of the full spectra of periodicities in the genomes of bacteria of both species. Their general and species-specific features have been identified, confirming the high classification potential of the used object description.
Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction
, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E ...(H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes.
Metal–organic frameworks (MOFs) are an emerging class of nanocarriers for drug delivery, owing to their tunable chemical functionality. Here we report ATP-responsive zeolitic imidazole framework-90 ...(ZIF-90) as a general platform for cytosolic protein delivery and CRISPR/Cas9 genome editing. The self-assembly of imidazole-2-carboxaldehyde and Zn2+ with protein forms ZIF-90/protein nanoparticles and efficiently encapsulates protein. It was found that, in the presence of ATP, the ZIF-90/protein nanoparticles are degraded to release protein due to the competitive coordination between ATP and the Zn2+ of ZIF-90. Intracellular delivery studies showed that the ZIF-90/protein nanoparticle can deliver a large variety of proteins into the cytosol, regardless of protein size and molecular weight. The delivery of cytotoxic RNase A efficiently prohibits tumor cell growth, while the effective delivery of genome-editing protein Cas9 knocks out the green fluorescent protein (GFP) expression of HeLa cells with efficiency up to 35%. Given the fact that ATP is upregulated in disease cells, it is envisaged that the ATP-responsive protein delivery will open up new opportunities for an advanced protein delivery and CRISPR/Cas9 genome editing for targeted disease treatment.
Comparative genome- and proteome-wide screens yield large amounts of data. To efficiently present such datasets and to simplify the identification of hits, the results are often presented in a type ...of scatterplot known as a volcano plot, which shows a measure of effect size versus a measure of significance. The data points with the largest effect size and a statistical significance beyond a user-defined threshold are considered as hits. Such hits are usually annotated in the plot by a label with their name. Volcano plots can represent ten thousands of data points, of which typically only a handful is annotated. The information of data that is not annotated is hardly or not accessible. To simplify access to the data and enable its re-use, we have developed an open source and online web tool with R/Shiny. The web app is named VolcaNoseR and it can be used to create, explore, label and share volcano plots ( https://huygens.science.uva.nl/VolcaNoseR ). When the data is stored in an online data repository, the web app can retrieve that data together with user-defined settings to generate a customized, interactive volcano plot. Users can interact with the data, adjust the plot and share their modified plot together with the underlying data. Therefore, VolcaNoseR increases the transparency and re-use of large comparative genome- and proteome-wide datasets.
GTex: Alles vernetzt Groß, Michael
Chemie in unserer Zeit,
12/2017, Letnik:
51, Številka:
6
Journal Article
Recenzirano
Das Netzwerk eines lebenden Organismus ist unglaublich kompliziert, wie wir in dieser Serie an ausgewählten Beispielen gesehen haben. Das menschliche Genom ist nur einer der Ansatzpunkte zur ...Erschließung der Zusammenhänge. Um medizinisch relevante Einblicke in die Ursachen von Krankheiten zu gewinnen, müssen wir verstehen lernen, wie das im ganzen Körper nahezu einheitliche Genom in verschiedenen Zellen und Geweben zu völlig verschiedenen Ausprägungen (Phänotypen) führt, und wie diese Verbindungen durch Mutationen beeinflusst werden. Diese gigantische Aufgabe geht das Gtex‐Projekt (Genotype Tissue Expression) an, das soeben eine umfassende Auswertung seiner Ergebnisse publiziert hat.
Beyond its extraordinary genome editing ability, the CRISPR-Cas systems have opened a new era of biosensing applications due to its high base resolution and isothermal signal amplification. However, ...the reported CRISPR-Cas sensors are largely only used for the detection of nucleic acids with limited application for non-nucleic-acid targets. To realize the full potential of the CRISPR-Cas sensors and broaden their applications for detection and quantitation of non-nucleic-acid targets, we herein report CRISPR-Cas12a sensors that are regulated by functional DNA (fDNA) molecules such as aptamers and DNAzymes that are selective for small organic molecule and metal ion detection. The sensors are based on the Cas12a-dependent reporter system consisting of Cas12a, CRISPR RNA (crRNA), and its single-stranded DNA substrate labeled with a fluorophore and quencher at each end (ssDNA-FQ), and fDNA molecules that can lock a DNA activator for Cas12a-crRNA, preventing the ssDNA cleavage function of Cas12a in the absence of the fDNA targets. The presence of fDNA targets can trigger the unlocking of the DNA activator, which can then activate the cleavage of ssDNA-FQ by Cas12a, resulting in an increase of the fluorescent signal detectable by commercially available portable fluorimeters. Using this method, ATP and Na+ have been detected quantitatively under ambient temperature (25 °C) using a simple and fast detection workflow (two steps and <15 min), making the fDNA-regulated CRISPR system suitable for field tests or point-of-care diagnostics. Since fDNAs can be obtained to recognize a wide range of targets, the methods demonstrated here can expand this powerful CRISPR-Cas sensor system significantly to many other targets and thus provide a new toolbox to significantly expand the CRISPR-Cas system into many areas of bioanalytical and biomedical applications.
Functional genomics assays based on high-throughput sequencing greatly expand our ability to understand the genome. Here, we define the ENCODE blacklist- a comprehensive set of regions in the human, ...mouse, worm, and fly genomes that have anomalous, unstructured, or high signal in next-generation sequencing experiments independent of cell line or experiment. The removal of the ENCODE blacklist is an essential quality measure when analyzing functional genomics data.
PDF
