Accession	GSE19906
Status	2010/6/7
Title	Global analysis of histone modification patterns on the latent KSHV episome
Organism	Human gammaherpesvirus 8
Experiment type	Genome binding/occupancy profiling by genome tiling array
Summary	Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of epigenetic modifications during latent infection with Kaposi's sarcoma associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). Using high resolution tiling microarrays in conjunction with immunprecipitation of methylated DNA (MeDIP) and modified histones (ChIP), we have determined global patterns of epigenetic modifications across the KSHV genome in several tumor-derived cell lines as well as de novo infected endothelial cells, revealing highly distinct landscapes of epigenetic modifications associated with latent KSHV infection. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolved slowly and thus are unlikely to govern latency early during the infection process. In contrast, we observed that latent histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, since both H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription despite of the simultaneous presence of activating marks. Our findings suggest that the epigenetic patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced. This dataset contains our ChIP-on-chip data; the MeDIP data are deposited in a separate dataset.
Samples	GSM ID Sample info Characteristics Description GSM498063 SLK_Input cell line:SLK; sample type:spot performance control; cell type:endothelial cells The Cy3 channel of this sample was used as a negative control to permanently flag spots which exhibit cross-hybridization with cellular DNA; there is no ratio data for this sample. GSM498066 BCBL1_H3K9me3 cell line:BCBL1; antibody:none; sample type:biological sample; cell type:B cells Analysis of H3K9me3 patterns in the PEL-derived cell line BCBL1 GSM498064 BCBL1_H3K9/14Ac cell line:BCBL1; antibody:H3K9/14Ac; sample type:biological sample; cell type:B cells Analysis of H3K9/14Ac patterns in the PEL-derived cell line BCBL1 GSM498067 BCBL1_H3K27me3 cell line:BCBL1; antibody:H3K27me3; sample type:biological sample; cell type:B cells Analysis of H3K27me3 patterns in the PEL-derived cell line BCBL1 GSM498064 BCBL1_H3K9/14Ac cell line:BCBL1; antibody:none; sample type:biological sample; cell type:B cells Analysis of H3K9/14Ac patterns in the PEL-derived cell line BCBL1 GSM498067 BCBL1_H3K27me3 cell line:BCBL1; antibody:none; sample type:biological sample; cell type:B cells Analysis of H3K27me3 patterns in the PEL-derived cell line BCBL1 GSM498065 BCBL1_H3K4me3 cell line:BCBL1; antibody:H3K4me3; sample type:biological sample; cell type:B cells Analysis of H3K4me3 patterns in the PEL-derived cell line BCBL1 GSM498065 BCBL1_H3K4me3 cell line:BCBL1; antibody:none; sample type:biological sample; cell type:B cells Analysis of H3K4me3 patterns in the PEL-derived cell line BCBL1 GSM498068 SLKP_H3K9/14Ac cell line:SLKP; antibody:H3K9/14Ac; sample type:biological sample; cell type:endothelial cells Analysis of H3K9/14Ac patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498066 BCBL1_H3K9me3 cell line:BCBL1; antibody:H3K9me3; sample type:biological sample; cell type:B cells Analysis of H3K9me3 patterns in the PEL-derived cell line BCBL1 GSM498068 SLKP_H3K9/14Ac cell line:SLKP; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K9/14Ac patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498069 SLKP_H3K4me3 cell line:SLKP; antibody:H3K4me3; sample type:biological sample; cell type:endothelial cells Analysis of H3K4me3 patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498069 SLKP_H3K4me3 cell line:SLKP; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K4me3 patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498070 SLKP_H3K9me3 cell line:SLKP; antibody:H3K9me3; sample type:biological sample; cell type:endothelial cells Analysis of H3K9me3 patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498070 SLKP_H3K9me3 cell line:SLKP; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K9me3 patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498071 SLKP_H3K27me3 cell line:SLKP; antibody:H3K27me3; sample type:biological sample; cell type:endothelial cells Analysis of H3K27me3 patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498071 SLKP_H3K27me3 cell line:SLKP; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K27me3 patterns in SLKP cells (long-term KSHV infected SLK cells) GSM498072 SLK5dpi_H3K4me3 cell line:SLK; antibody:H3K4me3; sample type:biological sample; cell type:endothelial cells Analysis of H3K4me3 patterns in de novo infected SLK cells at 5 days post-infection GSM498072 SLK5dpi_H3K4me3 cell line:SLK; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K4me3 patterns in de novo infected SLK cells at 5 days post-infection GSM498073 SLK5dpi_H3K9me3 cell line:SLK; antibody:H3K9me3; sample type:biological sample; cell type:endothelial cells Analysis of H3K9me3 patterns in de novo infected SLK cells at 5 days post-infection GSM498073 SLK5dpi_H3K9me3 cell line:SLK; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K9me3 patterns in de novo infected SLK cells at 5 days post-infection GSM498074 SLK5dpi_H3K27me3 cell line:SLK; antibody:H3K27me3; sample type:biological sample; cell type:endothelial cells Analysis of H3K27me3 patterns in de novo infected SLK cells at 5 days post-infection GSM498074 SLK5dpi_H3K27me3 cell line:SLK; antibody:none; sample type:biological sample; cell type:endothelial cells Analysis of H3K27me3 patterns in de novo infected SLK cells at 5 days post-infection
Platform	GPL9942  : HPI-AG KSHV 15k v. 3.0
Literature	20532208