title: Genome-wide identification of direct HBx genomic targets.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guerrieri
authors.affiliation: Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Belloni
authors.affiliation: Biocomputing Lab, Department of Physics, Sapienza University, Rome, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: D'Andrea
authors.affiliation: Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, Rome, 00161, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pediconi
authors.affiliation: Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy.|Biocomputing Lab, Department of Physics, Sapienza University, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Le Pera
authors.affiliation: INSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon, 69424, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Testoni
authors.affiliation: Department of Internal Medicine - DMISM, Sapienza University, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scisciani
authors.affiliation: INSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon, 69424, France.
authors.forename: Oceane
authors.initials: O
authors.lastname: Floriot
authors.affiliation: INSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon, 69424, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy.|Biocomputing Lab, Department of Physics, Sapienza University, Rome, Italy.|Istituto Pasteur Fondazione Cenci Bolognetti, Viale Regina Elena 291, Rome, 00161, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tramontano
authors.affiliation: Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, Rome, 00161, Italy. massimo.levrero@uniroma1.it.|INSERM U1052, Cancer Research Center of Lyon (CRCL), 151 cours Albert Thomas, Lyon, 69424, France. massimo.levrero@uniroma1.it.|Department of Internal Medicine - DMISM, Sapienza University, Viale del Policlinico 155, 00161, Rome, Italy. massimo.levrero@uniroma1.it.|Cancer Research Center of Lyon (CRCL) - INSERM U1052, 151 cours Albert Thomas, 69424, Lyon Cedex 03, France. massimo.levrero@uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Levrero
mesh_terms: D004705:Endocytosis; D023281:Genomics; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: ChIP-Seq; Epigenetics; HBx; Hepatitis B virus; miRNAs