Accession	GSE56144
Status	2014/4/1
Title	Site-Specific Association with Host and Viral Chromatin by KSHV LANA and its Reversal during Lytic Reactivation
Organism	Homo sapiens
Experiment type	Expression profiling by high throughput sequencing;Genome binding/occupancy profiling by high throughput sequencing
Summary	Latency-associated nuclear antigen (LANA), a multifunctional protein expressed by the Kaposi sarcoma-associated herpesvirus (KSHV) in latently-infected cells, is required for stable maintenance of the viral episome. This is mediated by two interactions: LANA binds to specific sequences (LBS1 and 2) on viral DNA, and also engages host histones, tethering the viral genome to host chromosomes in mitosis. LANA has also been suggested to affect host gene expression, but both the mechanism(s) and role of this dysregulation in KSHV biology remain unclear. Here we have examined LANA interactions with host chromatin on a genome-wide scale using ChIP-seq, and show that LANA predominantly targets human genes near their transcriptional start sites (TSSs). These host LANA-binding sites are generally found within transcriptionally active promoters and display striking overrepresentation of a consensus DNA sequence virtually identical to the LBS1 motif in KSHV DNA. Comparison of the ChIP-seq profile with whole transcriptome (RNA-seq) data reveals that few of the genes that are differentially regulated in latent infection are occupied by LANA at their promoters. This suggests that direct LANA binding to promoters is not the prime determinant of altered host transcription in KSHV-infected cells. Most surprisingly, the association of LANA to both host and viral DNA is strongly disrupted during the lytic cycle of KSHV. This disruption can be prevented by the inhibition of viral DNA synthesis, suggesting the existence of novel and potent regulatory mechanisms linked to either viral DNA replication or late gene expression.
Samples	GSM ID Sample info Characteristics Description GSM1359488 ChIPseq_LANA_iSLK219_rep2 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359489 ChIPseq_LANA_iSLK219_dox_rep2 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359490 ChIPseq_LANA_iSLK219_dox_PFA_rep2 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359491 ChIPseq_LANA_LEC_rep1 cell type:Dermal lymphatic endothelial cells; cell line:LEC; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for sample #10 GSM1359492 ChIPseq_LANA_LEC219_rep1 cell type:Dermal lymphatic endothelial cells; infection:rKSHV.219; cell line:LEC-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359493 ChIPseq_LANA_LEC_rep2 cell type:Dermal lymphatic endothelial cells; cell line:LEC; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for sample #12 GSM1359494 ChIPseq_LANA_LEC219_rep2 cell type:Dermal lymphatic endothelial cells; infection:rKSHV.219; cell line:LEC-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359495 ChIPseq_LANA_BEC cell type:Dermal blood endothelial cells; cell line:BEC; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for sample #14 GSM1359496 ChIPseq_LANA_BEC219 cell type:Dermal blood endothelial cells; infection:rKSHV.219; cell line:BEC-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359497 ChIPseq_LANA_BJAB cell type:Human Burkitt lymphoma B cells; cell line:BJAB; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for sample #16 GSM1359498 ChIPseq_LANA_BJAB219 cell type:Human Burkitt lymphoma B cells; infection:rKSHV.219; cell line:BJAB-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359499 ChIPseq_IgG_BCBL1 cell type:Primary effusion lymphoma B cells; infection:KSHV; cell line:BCBL-1; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for samples #18,19 GSM1359500 ChIPseq_LANA_BCBL1_rep1 cell type:Primary effusion lymphoma B cells; infection:KSHV; cell line:BCBL-1; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359501 ChIPseq_LANA_BCBL1_rep2 cell type:Primary effusion lymphoma B cells; infection:KSHV; cell line:BCBL-1; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359502 ChIPseq_H3K4me3_iSLK cell type:Kidney epithelial cells; cell line:iSLK; chip antibody:H3K4me3 (Abcam, ab8580) - GSM1359503 ChIPseq_H3K4me3_iSLK219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:H3K4me3 (Abcam, ab8580) - GSM1359504 ChIPseq_H3K4me3_LEC cell type:Dermal lymphatic endothelial cells; cell line:LEC; chip antibody:H3K4me3 (Abcam, ab8580) - GSM1359505 ChIPseq_H3K4me3_LEC219 cell type:Dermal lymphatic endothelial cells; infection:rKSHV.219; cell line:LEC-219; chip antibody:H3K4me3 (Abcam, ab8580) - GSM1359506 ChIPseq_PolII_iSLK219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:Pol II (Santa Cruz Biotechnology, sc-899 X) - GSM1359507 ChIPseq_H3K36me3_iSLK219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:H3K36me3 (Abcam, ab9050) - GSM1359508 ChIPseq_H3K27me3_iSLK219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:H3K27me3 (Millipore, 07-449) - GSM1359509 ChIPseq_IgG_iSLK219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:IgG (Millipore, pp64b) ChIPseq peak calling control data set for sample #20,21 GSM1359510 ChIPseq_IgG_LEC219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:LEC-219; chip antibody:IgG (Millipore, pp64b) ChIPseq peak calling control data set for sample #22,23 GSM1359511 ChIPseq_input_iSLK219 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219 Sequencing control GSM1359512 RNAseq_LEC_rep1 cell type:Dermal lymphatic endothelial cells; cell line:LEC - GSM1359513 RNAseq_LEC219_rep1 cell type:Dermal lymphatic endothelial cells; infection:rKSHV.219; cell line:LEC-219 - GSM1359514 RNAseq_LEC_rep2 cell type:Dermal lymphatic endothelial cells; cell line:LEC - GSM1359515 RNAseq_LEC219_rep2 cell type:Dermal lymphatic endothelial cells; infection:rKSHV.219; cell line:LEC-219 - GSM1359483 ChIPseq_LANA_iSLK_rep1 cell type:Kidney epithelial cells; cell line:iSLK; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for samples #2,3,4 GSM1359484 ChIPseq_LANA_iSLK219_rep1 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359485 ChIPseq_LANA_iSLK219_dox_rep1 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359486 ChIPseq_LANA_iSLK219_dox_PFA_rep1 cell type:Kidney epithelial cells; infection:rKSHV.219; cell line:iSLK-219; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) - GSM1359487 ChIPseq_LANA_iSLK_rep2 cell type:Kidney epithelial cells; cell line:iSLK; chip antibody:LANA (Advanced Biotechnologies, 13-210-100) ChIPseq peak calling control data set for samples #6,7,8
Platform	GPL9115  GPL16791  : Illumina Genome Analyzer II (Homo sapiens);Illumina HiSeq 2500 (Homo sapiens)
Literature	24696474
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