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Series GSE113879 Query DataSets for GSE113879
Status Public on Feb 07, 2019
Title Mapping the heterogeneity of histone modifications on hepatitis B virus-DNA using liver needle biopsies obtained from chronically infected patients
Organisms Homo sapiens; Hepatitis B virus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Covalently closed circular DNA (cccDNA) forms the basis for replication and persistence of hepatitis B virus (HBV) in the chronically infected liver. We have previously shown through the analysis of de novo HBV infected cell lines that viral transcription is subject to regulation by posttranslational modifications (PTMs) of histone proteins bound to cccDNA. We now report the successful adaptation of this ChIPseq approach for the analysis of fine-needle patient liver biopsy specimens to investigate the role of histone PTMs in chronically HBV-infected patients. Using 18 specimens from patients in different stages of chronic HBV infection our work shows that the profile of histone PTMs in chronic infection is more nuanced than observed in our previous work largely focused on acute infection in in vitro models. Specifically, we find that the majority of recovered HBV sequences are associated with the activating histone PTM H3K4me3, in line with our previous findings. We further find that the striking interpatient variability of its deposition in this patient cohort is linked to viral transcription and patient HBeAg status. Unexpectedly, we detect a significant localized deposition of the inhibitory histone PTM H3K9me3 on HBV-DNA in select patient biopsies which was not observed previously. Altogether, our results show that current in vitro models of HBV infection are unable to fully recapitulate the complex epigenetic landscape of chronic HBV infection observed in vivo and demonstrate that fine needle liver biopsy specimens can provide sufficient material to further investigate the interaction of viral and host proteins on HBV-DNA.
Overall design 18 liver biopsy specimens were analyzed with input, H3K4me3, and H3K27me3-ChIP for all of them as well as H3 and H3K9me3 ChIPs for select biopsies, as indicated in sample descriptions. Additionally, in vitro infected primary human hepatocytes and cell lines with or without known integrated HBV-DNA (HepG2-hNTCP, HepG2-HBV, Hep3B, PLC/PRF/5) were included as controls. All ChIPseq results for H3, H3K4me3, H3K9me3 were obtained in duplicate with independently constructed libraries. Input and H3K27me3 sequencing results were replicated for 5 and 2 biopsies, respectively. All sequencing results from in vitro models were obtained in duplicate. An overview as well as the average HBV-derived readcounts normalized to 106 total reads are found in avgRPM.xlsx
Contributor(s) Flecken T, Meier M, Skewes-Cox P, Barkan DT, Heim MH, Wieland SF, Holdorf MM
Citation(s) 30787147
Submission date Apr 30, 2018
Last update date Apr 29, 2019
Contact name Tobias Flecken
Organization name Novartis Institutes for Biomedical Research
Department Infectious Diseases
Street address 5300 Chiron Way
City Emeryville
State/province CA
ZIP/Postal code 94608
Country USA
Platforms (2)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL24950 Illumina MiSeq (Hepatitis B virus; Homo sapiens)
Samples (179)
GSM3122303 b880-input_1
GSM3122304 b880-input_2
GSM3122305 b880-H3-ChIP_1
BioProject PRJNA454318
SRA SRP144085

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE113879_RAW.tar 390.0 Kb (http)(custom) TAR (of WIG)
GSE113879_avgRPM.xlsx 14.2 Kb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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