Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hepatitis B Virus Episome DNA Localizes To the Vicinity of Chromosome 19 In 3D Host Genome Upon Infection

ABSTRACT: Hepatitis B virus (HBV) infects 240 million people worldwide. The infection requires establishment and persistence of a viral episome, the covalently closed circular (ccc) DNA, in the nucleus. Here we studied cccDNA spatial localization in the 3D host genome by using chromosome conformation capture based sequencing analysis and fluorescence in situ hybridization (FISH). We show cccDNA is not randomly distributed in host nucleus, rather, it is preferentially accumulated at specialized areas, particularly in regions close to chromosome 19 (chr.19). Activation of cccDNA appears to be associated with its re-localization from a heterochromatin hub pre-established by 5 regions of chr.19 to transcriptionally active regions formed by chromosomes in close proximity to chr.19 including chr. 16, 17, 20, 22. This active versus inactive positioning at discrete regions of host genome is primarily controlled by viral HBx protein and host factors including the structural maintenance of chromosomes protein 5/6 (SMC5/6) complex.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145150 | GEO | 2021/07/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [Hi-C]

Project description:The Structural Maintenance of Chromosome (SMC) protein complexes cohesin, condensin and the Smc5/6 complex (Smc5/6) are essential for chromosome function. At the molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates chromosome loops in interphase, and condensin compacts mitotic chromosomes. However, the role of Smc5/6’s recently discovered DNA loop extrusion activity is unknown. Here, we uncover that Smc5/6 controls the spatial organization of supercoiled chromosomal regions. The results show that Smc5/6 associates with transcription-induced positively supercoiled chromosomal DNA at cohesin-dependent chromosome loop boundaries. Mechanistically, single-molecule imaging reveals that dimers of Smc5/6 specifically recognize the tip of positively supercoiled DNA plectonemes, and efficiently initiates loop extrusion to gather the supercoiled DNA into a large plectonemic loop. Finally, Hi-C analysis shows that Smc5/6 links chromosomal regions containing transcription-induced positive supercoiling in cis. Altogether, our findings indicate that Smc5/6 controls the three-dimensional organization of chromosomes by recognizing and initiating loop extrusion on positively supercoiled DNA.

2024-01-30 | GSE235558 | GEO

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [RNA-seq]

2024-01-30 | GSE235559 | GEO

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [ChIP-seq]

2024-01-30 | GSE235557 | GEO

Binding of Nucleolin to HBV cccDNA

Project description:Covalently closed circular DNA (cccDNA) forms the basis for replication and persistence of hepatitis B virus (HBV) in the chronically infected liver. In this study we sought to identify host factors interacting with the HBV genome. Nucleolin (Ncl) was identified as a potential interactor of HBV cccDNA. This interaction was veriefied using an established ChIPseq protocol. The data show that Ncl binds cccDNA albeit at lower levels than HBcAg. Ncl deposition occurs across the genome without a clear localization and a variable pattern of deposition between experiments. This verifies the interaction of Ncl with HBV-cccDNA.

2021-12-31 | GSE123715 | GEO

Silencing of unintegrated HIV-1 by SLF2 and the SMC5/6 complex

Project description:Silencing of nuclear DNA is an essential feature of the innate immune response to invading pathogens. Early in lentiviral infection, unintegrated viral cDNA accumulates in the nucleus, yet remains poorly expressed. In HIV-1-like lentiviruses, the Vpr accessory protein enhances unintegrated viral DNA expression, suggesting Vpr antagonises cellular restriction. We previously showed how Vpr remodels the host proteome, identifying multiple cellular targets. We now screen these using a targeted CRISPR-Cas9 library, identifying SMC5-SMC6 complex localization factor 2 (SLF2) as the Vpr target responsible for silencing unintegrated HIV-1. SLF2 recruits the SMC5/6 complex to unintegrated lentiviruses, and depletion of SLF2, or the SMC5/6 complex, increases viral expression. Using ATAC-seq, we show that Vpr-mediated SLF2 depletion increases chromatin accessibility of unintegrated virus, suggesting the SMC5/6 complex compacts viral chromatin to silence gene expression. This work implicates the SMC5/6 complex in nuclear immunosurveillance of extrachromosomal DNA and defines an evolutionarily conserved antagonism by Vpr.

2021-03-01 | GSE156630 | GEO

SMC5/6 facilitates joint molecule resolution and stepwise loss of cohesin to promote meiotic chromosome segregation

Project description:During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Diminished Smc5/6 function causes severe defects in nuclear division, but the underlying causes of these defects remain unclear. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of joint-molecule intermediates. Furthermore, we find that Smc5/6 specifically promotes resolution of joint molecules via the XPF-family endonuclease, Mus81-Mms4Eme1. We propose that Smc5/6 acts as a chaperone for M-bM-^@M-^XmitoticM-bM-^@M-^Y-like recombination processes during meiosis. ChIP-chip was used to compare Smc5 localization in wild-type and spo11 strains

2013-12-27 | E-GEOD-44852 | biostudies-arrayexpress

A nucleosome switch primes Hepatitis B Virus infection [Mnase-Seq]

Project description:Chronic hepatitis B virus (HBV) infection is an incurable global health threat capable of causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent chromosome, cccDNA, consisting of the circular viral genome and host histones. The first viral protein expressed, HBx, induces degradation of a host silencing factor to facilitate infection. However, the relationship between cccDNA’s chromatin and early HBx transcription state remains poorly understood. Using reconstituted viral chromosomes, we found that nucleosomes in cccDNA drive HBx transcription. We corroborated these findings in cells and further showed that chromatin destabilizing drugs inhibit viral transcription and antigen expression in hepatocytes. Our results shed new light on a long-standing paradox and represent a novel therapeutic avenue for the treatment of chronic HBV.

2023-03-03 | GSE225715 | GEO

A nucleosome switch primes Hepatitis B Virus infection [RNA-Seq]

2023-03-03 | GSE225714 | GEO

Testicular germ cell tumor susceptibility genes from the consomic 129.MOLF-Chr19 mouse strain

Project description:Chromosome substitution strains (CSS or consomic strains) are useful for mapping phenotypes to chromosomes. However, huge efforts are needed to identify the gene(s) responsible for the phenotype in the complex context of the chromosome. Here, we report the identification of candidate disease genes from a CSS using a combination of genetic and genomic approaches as well as by using knowledge about the germ cell tumor disease etiology. We utilized the CSS, 129.MOLF-Chr 19 chromosome substitution strain (or M19), in which males develop germ cell tumors of the testes at an extremely high rate. We are able to identify 3 protein-coding genes and 1 microRNA on chromosome 19 that have previously not been implicated to be testicular tumor susceptibility genes. Our findings suggest that changes in gene expression levels in the gonadal tissues of multiple genes from Chr 19 likely contribute to the high TGCT incidence of the M19 strain. Our data advances the use of CSS to identify disease susceptibility genes and demonstrates that the 129.MOLF-Chr 19 strain serves as a useful model to elucidate the genetics and biology of germ cell transformation and tumor development.

2009-01-13 | GSE14354 | GEO

Host genomic regions susceptible to damage during H. pylori infection

Project description:We identify here host genomic regions that are more likely to be damaged during an infection with the human gastirc pathogen Helicobacter pylori and characterize underlying features of them. By ChIP-seq we obtained global information about the localization of the DNA-damage marker H2AXpS139. We used 20 ng of immunoprecipitated DNA of the human gastric cell line AGS to produce 240 mio sequence reads in total and compared the damage-pattern of 6 h and 19 h infected cells with that of 10 Gy irradiated ones. While the overall levesl of DNA damage wetre similar in terms of broken DNA and accumulation of H2AXpS139, infection-induced damage clearly accumulates towards the ends of chromosomal arms, namely telomere-proximal and close to centromeres, it also enriches mainly in genic and especially in transcribed regions. We show, taht this damage pattern is unique to the infection, occurs also in human non-transformed gastric epithelial cells and shows some correlation with previously identified cancer-related genes. Examination of a DNA-damage induced histone modification from four different conditions.

2015-05-18 | E-GEOD-55699 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data