Genome-wide identification of direct HBx genomic targets

Abstract : AbstractBackgroundThe 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.ResultsChIP-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.ConclusionsOur 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.
Type de document :
Article dans une revue
BMC Genomics, BioMed Central, 2016, 18 (1), pp.184. 〈10.1186/s12864-017-3561-5〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-01470815
Contributeur : Bmc Bmc <>
Soumis le : vendredi 17 février 2017 - 18:03:04
Dernière modification le : vendredi 23 mars 2018 - 16:43:00
Document(s) archivé(s) le : jeudi 18 mai 2017 - 15:20:15

Fichiers

12864_2017_Article_3561.pdf
Publication financée par une institution

Identifiants

Collections

Citation

Francesca Guerrieri, Laura Belloni, Daniel D’andrea, Natalia Pediconi, Loredana Le Pera, et al.. Genome-wide identification of direct HBx genomic targets. BMC Genomics, BioMed Central, 2016, 18 (1), pp.184. 〈10.1186/s12864-017-3561-5〉. 〈inserm-01470815〉

Partager

Métriques

Consultations de la notice

34

Téléchargements de fichiers

137