Accession	GSE68402
Status	2015/10/8
Title	Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin conformation amenable to epigenetic manipulation
Organism	Homo sapiens
Experiment type	Genome binding/occupancy profiling by high throughput sequencing
Summary	Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative since it does not eliminate nuclear HBV cccDNA, the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target the transcriptional regulation of cccDNA would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes and from HBV infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome, and surprisingly very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection.
Samples	GSM ID Sample info Characteristics Description GSM1670894 HiSeq_HepG2_Nuc cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2 Nucleosome input for Sample 2-4 GSM1670895 HiSeq_HepG2_H3K4me3 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K4me3 (Abcam ab8580) - GSM1670896 HiSeq_HepG2_Pol2 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:RNA Polymerase 2 (Abcam ab817) - GSM1670897 HiSeq_HepG2_H3K27ac cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K27ac (Abcam ab4729) - GSM1670898 MiSeq_HepG2_Nuc cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2 Nucleosome input for Sample 6-12 GSM1670899 MiSeq_HepG2_H3K4me3 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K4me3 (Abcam ab8580) - GSM1670900 MiSeq_HepG2_H3K27ac cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K27ac (Abcam ab4729) - GSM1670901 MiSeq_HepG2_H3K36me3 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K36me3 (Millipore ABE435) - GSM1670902 MiSeq_HepG2_H3K122ac cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K122ac (Abcam ab33309) - GSM1670903 MiSeq_HepG2_H3K9me3 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K9me3 (Abcam ab8898) - GSM1670904 MiSeq_HepG2_H3K27me3 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:H3K27me3 (Millipore 07-449) - GSM1670905 MiSeq_HepG2_Pol2 cell type:hepatoblastoma cells; infection:HBV (ayw); cell line:HepG2; chip antibody:RNA Polymerase 2 (Abcam ab817) - GSM1670906 MiSeq_PHH_Nuc cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes Nucleosome input for Sample 14-19 GSM1670907 MiSeq_PHH_H3K4me3 cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes; chip antibody:H3K4me3 (Abcam ab8580) - GSM1670908 MiSeq_PHH_H3K27ac cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes; chip antibody:H3K27ac (Abcam ab4729) - GSM1670909 MiSeq_PHH_H3K36me3 cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes; chip antibody:H3K36me3 (Millipore ABE435) - GSM1670910 MiSeq_PHH_H3K122ac cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes; chip antibody:H3K122ac (Abcam ab33309) - GSM1670911 MiSeq_PHH_H3K27me3 cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes; chip antibody:H3K27me3 (Millipore 07-449) - GSM1670912 MiSeq_PHH_Pol2 cell type:primary hepatocytes; infection:HBV (ayw); cell line:primary hepatocytes; chip antibody:RNA Polymerase 2 (Abcam ab817) - GSM1670913 MiSeq_Liver_Nuc cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue Nucleosome input for Sample 21-26 GSM1670914 MiSeq_Liver_H3K4me3 cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue; chip antibody:H3K4me3 (Abcam ab8580) - GSM1670915 MiSeq_Liver_H3K27ac cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue; chip antibody:H3K27ac (Abcam ab4729) - GSM1670916 MiSeq_Liver_H3K36me3 cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue; chip antibody:H3K36me3 (Millipore ABE435) - GSM1670917 MiSeq_Liver_H3K122ac cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue; chip antibody:H3K122ac (Abcam ab33309) - GSM1670918 MiSeq_Liver_H3K27me3 cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue; chip antibody:H3K27me3 (Millipore 07-449) - GSM1670919 MiSeq_Liver_Pol2 cell type:liver tissue; infection:HBV (endogenous); cell line:liver tissue; chip antibody:RNA Polymerase 2 (Abcam ab817) -
Platform	GPL15520  GPL16791  : Illumina MiSeq (Homo sapiens);Illumina HiSeq 2500 (Homo sapiens)
Literature	26438841
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