Le Pera, Loredana
KAUST Grant NumberKUKI1-012-43
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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.
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.
SponsorsThis 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.