Short- and long-range cis interactions between integrated HPV genomes and cellular chromatin dysregulate host gene expression in early cervical carcinogenesis

Development of cervical cancer is directly associated with integration of human papillomavirus (HPV) genomes into host chromosomes and subsequent modulation of HPV oncogene expression, which correlates with multi-layered epigenetic changes at the integrated HPV genomes. However, the process of integration itself and dysregulation of host gene expression at sites of integration in our model of HPV16 integrant clone natural selection has remained enigmatic. We now show, using a state-of-the-art ‘HPV integrated site capture’ (HISC) technique, that integration likely occurs through microhomology-mediated repair (MHMR) mechanisms via either a direct process, resulting in host sequence deletion (in our case, partially homozygously) or via a ‘looping’ mechanism by which flanking host regions become amplified. Furthermore, using our ‘HPV16-specific Region Capture Hi-C’ technique, we have determined that chromatin interactions between the integrated virus genome and host chromosomes, both at short- (<500 kbp) and long-range (>500 kbp), appear to drive local host gene dysregulation through the disruption of host:host interactions within (but not exceeding) host structures known as topologically associating domains (TADs). This mechanism of HPV-induced host gene expression modulation indicates that integration of virus genomes near to or within a ‘cancer-causing gene’ is not essential to influence their expression and that these modifications to genome interactions could have a major role in selection of HPV integrants at the early stage of cervical neoplastic progression.

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Three-dimensional interactions between integrated HPV genomes and cellular chromatin dysregulate host gene expression in early cervical carcinogenesis

10.1101/2021.02.03.429496 ◽

2021 ◽

Author(s):

Ian J Groves ◽

Emma LA Drane ◽

Marco Michalski ◽

Jack M Monahan ◽

Cinzia G Scarpini ◽

...

Keyword(s):

Gene Expression ◽

Early Stage ◽

Three Dimensional ◽

Virus Genome ◽

Host Gene ◽

Neoplastic Progression ◽

Host Gene Expression ◽

Gene Dysregulation ◽

Sequence Deletion ◽

Virus Genomes

AbstractDevelopment of cervical cancer is directly associated with integration of human papillomavirus (HPV) genomes into host chromosomes and subsequent modulation of HPV oncogene expression, which correlates with multi-layered epigenetic changes at the integrated HPV genomes. However, the process of integration itself and dysregulation of host gene expression at sites of integration in our model of HPV16 integrant clone natural selection has remained enigmatic. We now show, using a state-of-the-art ‘HPV integrated site capture’ (HISC) technique, that integration likely occurs through microhomology-mediated repair (MHMR) mechanisms via either a direct process, resulting in host sequence deletion (in our case, partially homozygously) or via a ‘looping’ mechanism by which flanking host regions become amplified. Furthermore, using our ‘HPV16-specific Region Capture Hi-C’ technique, we have determined that three-dimensional (3D) interactions between the integrated virus genome and host chromosomes, both at short- (<500 kbp) and long-range (>500 kbp), appear to drive host gene dysregulation through the disruption of local host:host 3D interactions known as topologically associating domains (TADs). This mechanism of HPV-induced host gene expression modulation indicates that integration of virus genomes near to or within a ‘cancer-causing gene’ is not essential to influence such genes within an entire TAD and that these modifications to 3D interactions could have a major role in selection of HPV integrants at the early stage of cervical neoplastic progression.

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Transcript imaging and candidate gene strategy for the characterisation of Prunus/PPV interactions

Plant Protection Science ◽

10.17221/10332-pps ◽

2002 ◽

Vol 38 (SI 1 - 6th Conf EFPP 2002) ◽

pp. S112-S116 ◽

Cited By ~ 3

Author(s):

V. Decroocq ◽

V. Schurdi-Levraud ◽

D. Wawrzyńczak ◽

J.P. Eyquard ◽

M. Lansac

Keyword(s):

Gene Expression ◽

Candidate Gene ◽

Host Plant ◽

Candidate Genes ◽

Infected Plant ◽

Virus Genome ◽

Host Gene ◽

Plum Pox Virus ◽

Virus Species ◽

Host Gene Expression

Plum pox virus (PPV), the causing agent of the sharka disease, belongs to the genus Potyvirus that contains the largest number of virus species infecting plants. The virus genome has been extensively characterised and sequenced. However, few data are available on its interactions with the host plant, Prunus. In this study, we are focusing on the cloning and characterisation of any candidate genes involved in the expression of the resistance/susceptibility trait and any polymorphic genes putatively involved in the trait variation. In order to clone candidate genes, two main approaches are currently developed: the homology cloning of genes presumed to affect the resistance/susceptibility trait and the differential screening of cDNA pools corresponding to infected and non-infected plant material. The second approach is based on the transcript imaging of the host plant response to PPV infection. Previously, it has been shown that infection by a potyvirus is associated with specific changes in host gene expression, mainly down-regulation, while the expression of some genes remained unchanged. Thereby, in the differential display approach combined to further characterisation of candidate gene expression, we aim to monitor host gene expression in response to the virus and to describe a highly regulated interaction between the Prunus host plant and the infecting Plum pox virus.

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Faculty Opinions recommendation of Transcriptome analysis of a cnidarian-dinoflagellate mutualism reveals complex modulation of host gene expression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014151.370912 ◽

2006 ◽

Author(s):

Nico M van Straalen

Keyword(s):

Gene Expression ◽

Transcriptome Analysis ◽

Host Gene ◽

Host Gene Expression ◽

Complex Modulation

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Publisher Correction: Exogenously overexpressed intronic long noncoding RNAs activate host gene expression by affecting histone modification in Arabidopsis

Scientific Reports ◽

10.1038/s41598-020-79079-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Zhang-Wei Liu ◽

Nan Zhao ◽

Yin-Na Su ◽

Shan-Shan Chen ◽

Xin-Jian He

Keyword(s):

Gene Expression ◽

Histone Modification ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Host Gene ◽

Host Gene Expression

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Regulation of host gene expression during nodule development in soybeans

Nitrogen Fixation ◽

10.1007/978-1-4684-6432-0_60 ◽

1990 ◽

pp. 701-708 ◽

Cited By ~ 2

Author(s):

C. Sengupta-Gopalan ◽

E. Estabrook ◽

H. Gambliel ◽

W. Nirunsuksiri ◽

H. Richter

Keyword(s):

Gene Expression ◽

Host Gene ◽

Nodule Development ◽

Host Gene Expression

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Wolbachia infection may improve learning and memory capacity of Drosophila by altering host gene expression through microRNA

Insect Biochemistry and Molecular Biology ◽

10.1016/j.ibmb.2018.11.007 ◽

2019 ◽

Vol 106 ◽

pp. 47-54 ◽

Cited By ~ 3

Author(s):

Jie Bi ◽

Ya Zheng ◽

Rui-Fang Wang ◽

Hui Ai ◽

Paula R. Haynes ◽

...

Keyword(s):

Gene Expression ◽

Learning And Memory ◽

Wolbachia Infection ◽

Memory Capacity ◽

Host Gene ◽

Host Gene Expression

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Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

mBio ◽

10.1128/mbio.00145-21 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Lauren E. Fuess ◽

Stijn den Haan ◽

Fei Ling ◽

Jesse N. Weber ◽

Natalie C. Steinel ◽

...

Keyword(s):

Gene Expression ◽

Microbial Communities ◽

Gut Microbiome ◽

Alpha Diversity ◽

Host Immunity ◽

Host Gene ◽

Microbiota Composition ◽

Host Gene Expression ◽

Microbiome Composition ◽

Immune Genes

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.

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Microbiota Modulates Host Gene Expression via MicroRNAs

Gastroenterology ◽

10.1016/s0016-5085(11)62754-6 ◽

2011 ◽

Vol 140 (5) ◽

pp. S-663 ◽

Cited By ~ 2

Author(s):

Guillaume Dalmasso ◽

Hang Thi Thu Nguyen ◽

Yutao Yan ◽

Hamed Laroui ◽

Moiz A. Charania ◽

...

Keyword(s):

Gene Expression ◽

Host Gene ◽

Host Gene Expression

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Abstract 19222: Hypoxia Regulated Circular RNAs Control Endothelial Cell Functions (Best of Basic Science Abstract)

Circulation ◽

10.1161/circ.132.suppl_3.19222 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Andreas W Heumüller ◽

Jes-Niels Boeckel ◽

Nicolas Jaé ◽

Yuliya Ponomareva ◽

Wei Chen ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Network Formation ◽

Rare Event ◽

Expression Regulation ◽

Host Gene ◽

Circular Rnas ◽

Host Gene Expression ◽

Go Annotation ◽

Cell Functions

Circular RNAs (circRNAs) are non-coding RNAs generated by back-splicing. Back-splicing has been considered as a rare event, but circRNAs were recently found to be abundantly expressed among a variety of human cells and tissues. Nevertheless, the expressional regulation, processing and biological functions of circRNAs are largely unknown. Cytoplasmic circRNAs can bind and trap microRNAs, whereas nuclear circRNAs may affect host gene expression. However, the expression, regulation and functions of circRNAs in endothelial cells have not been determined so far. In this study, basal expression and regulation of circRNAs by hypoxia in human umbilical endothelial cells (HUVEC) were analyzed using deep sequencing. Among the identified 7,388 circRNAs, 2,875 had not been annotated before. We further validated the expression of 40 selected circRNAs by RT-PCR and found that the majority is resistant to RNase R digestion, lacks polyadenylation and is localized to the cytoplasm. Cloning and subsequent sequencing validated the newly generated back splice sites for selected circRNAs. Furthermore, analysis of RNA-seq data revealed that circRNAs, particularly the cytoplasmatic circular RNA cZNF292, are significantly regulated by hypoxia in HUVECs. The siRNA-mediated knockdown of HIF-1α had no effect on cZNF292 induction under hypoxia, suggesting a HIF-1α independent regulation. Most importantly, siRNA-mediated knockdown of cZNF292 significantly reduced spheroid sprouting and network formation of endothelial cells. Furthermore, knockdown of cZNF292 had no effect on its host gene expression. Exon array analysis after cZNF292 knockdown revealed a significant expressional upregulation of 167 as well as a significant expressional downregulation of 123 genes of which most were associated with metabolic processes according to GO annotation. Analysis of Ago-HITS-CLIP data revealed no putative miR-binding sites, suggesting that cZNF292 does not act as a miR-sponge. Taken together, we show for the first time the expression, regulation and function of circRNAs in endothelial cells. The circRNA cZNF292 is regulated by hypoxia and has an important angiogenic function in endothelial cells.

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