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.

Genome-wide identification of direct HBx genomic targets / Guerrieri, F.; Belloni, L.; D'Andrea, D.; Pediconi, N.; Le Pera, L.; Testoni, B.; Scisciani, C.; Floriot, O.; Zoulim, F.; Tramontano, A.; Levrero, M.. - In: BMC GENOMICS. - ISSN 1471-2164. - 18:1(2017). [10.1186/s12864-017-3561-5]

Genome-wide identification of direct HBx genomic targets

Guerrieri F.;Belloni L.;D'Andrea D.;Pediconi N.;Le Pera L.;Scisciani C.;Tramontano A.;Levrero M.
2017

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.
2017
chip-seq; epigenetics; hbx; hepatitis b virus; mirnas; endocytosis; hep g2 cells; hepatitis b virus; host-pathogen interactions; humans; micrornas; trans-activators; viral regulatory and accessory proteins; virus replication; genomics
01 Pubblicazione su rivista::01a Articolo in rivista
Genome-wide identification of direct HBx genomic targets / Guerrieri, F.; Belloni, L.; D'Andrea, D.; Pediconi, N.; Le Pera, L.; Testoni, B.; Scisciani, C.; Floriot, O.; Zoulim, F.; Tramontano, A.; Levrero, M.. - In: BMC GENOMICS. - ISSN 1471-2164. - 18:1(2017). [10.1186/s12864-017-3561-5]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1480004
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