Handle URI:
http://hdl.handle.net/10754/623548
Title:
Genome-wide identification of direct HBx genomic targets
Authors:
Guerrieri, Francesca; Belloni, Laura; D’Andrea, Daniel; Pediconi, Natalia; Le Pera, Loredana; Testoni, Barbara; Scisciani, Cecilia; Floriot, Oceane; Zoulim, Fabien; Tramontano, Anna; Levrero, Massimo
Abstract:
Background The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV. Results ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication. Conclusions Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication.
Citation:
Guerrieri F, Belloni L, D’Andrea D, Pediconi N, Le Pera L, et al. (2017) Genome-wide identification of direct HBx genomic targets. BMC Genomics 18. Available: http://dx.doi.org/10.1186/s12864-017-3561-5.
Publisher:
Springer Nature
Journal:
BMC Genomics
KAUST Grant Number:
KUKI1-012-43
Issue Date:
17-Feb-2017
DOI:
10.1186/s12864-017-3561-5
Type:
Article
ISSN:
1471-2164
Sponsors:
This work was supported by grants from: the Italian Ministry of University and Research (MIUR-FIRB), the Italian Ministry of Health (Ricerca Finalizzata: RF 2010–2317822), the CARIPLO Foundation, the University of Lyon-St Etienne (PALSE PROGRAM), the Agence National de la Recherche (ANR@TRACTION), the Center for Life NanoSciences of the Italian Institute of Technology (CLNS-IIT) to ML; ANRS to ML and FZ; KAUST [KUKI1-012-43] and Epigenomics Flagship Project – EPIGEN to AT; DevWeCan French Laboratories of Excellence Network (Labex, Grant #ANR-10-LABX-61) to FZ; the Gilead Sciences Research Scholars Program in Liver Diseases to LB. FG, LL and LB are recipients of research contracts from IIT.
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Full metadata record

DC FieldValue Language
dc.contributor.authorGuerrieri, Francescaen
dc.contributor.authorBelloni, Lauraen
dc.contributor.authorD’Andrea, Danielen
dc.contributor.authorPediconi, Nataliaen
dc.contributor.authorLe Pera, Loredanaen
dc.contributor.authorTestoni, Barbaraen
dc.contributor.authorScisciani, Ceciliaen
dc.contributor.authorFloriot, Oceaneen
dc.contributor.authorZoulim, Fabienen
dc.contributor.authorTramontano, Annaen
dc.contributor.authorLevrero, Massimoen
dc.date.accessioned2017-05-15T10:35:07Z-
dc.date.available2017-05-15T10:35:07Z-
dc.date.issued2017-02-17en
dc.identifier.citationGuerrieri F, Belloni L, D’Andrea D, Pediconi N, Le Pera L, et al. (2017) Genome-wide identification of direct HBx genomic targets. BMC Genomics 18. Available: http://dx.doi.org/10.1186/s12864-017-3561-5.en
dc.identifier.issn1471-2164en
dc.identifier.doi10.1186/s12864-017-3561-5en
dc.identifier.urihttp://hdl.handle.net/10754/623548-
dc.description.abstractBackground The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV. Results ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication. Conclusions Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication.en
dc.description.sponsorshipThis work was supported by grants from: the Italian Ministry of University and Research (MIUR-FIRB), the Italian Ministry of Health (Ricerca Finalizzata: RF 2010–2317822), the CARIPLO Foundation, the University of Lyon-St Etienne (PALSE PROGRAM), the Agence National de la Recherche (ANR@TRACTION), the Center for Life NanoSciences of the Italian Institute of Technology (CLNS-IIT) to ML; ANRS to ML and FZ; KAUST [KUKI1-012-43] and Epigenomics Flagship Project – EPIGEN to AT; DevWeCan French Laboratories of Excellence Network (Labex, Grant #ANR-10-LABX-61) to FZ; the Gilead Sciences Research Scholars Program in Liver Diseases to LB. FG, LL and LB are recipients of research contracts from IIT.en
dc.publisherSpringer Natureen
dc.subjectHepatitis B virusen
dc.subjectHBxen
dc.subjectEpigeneticsen
dc.subjectmiRNAsen
dc.subjectChIP-Seqen
dc.titleGenome-wide identification of direct HBx genomic targetsen
dc.typeArticleen
dc.identifier.journalBMC Genomicsen
dc.contributor.institutionCenter for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome 00161, Italyen
dc.contributor.institutionBiocomputing Lab, Department of Physics, Sapienza University, Rome, Italyen
dc.contributor.institutionDepartment of Molecular Medicine, Sapienza University, Viale Regina Elena 291, Rome 00161, Italyen
dc.contributor.institutionINSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon 69424, Franceen
dc.contributor.institutionDepartment of Internal Medicine - DMISM, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italyen
dc.contributor.institutionIstituto Pasteur Fondazione Cenci Bolognetti, Viale Regina Elena 291, Rome 00161, Italyen
dc.contributor.institutionCancer Research Center of Lyon (CRCL) - INSERM U1052, 151 cours Albert Thomas, 69424 Lyon Cedex 03, Franceen
kaust.grant.numberKUKI1-012-43en
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