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Series GSE56144 Query DataSets for GSE56144
Status Public on Apr 01, 2014
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.
Overall design Profiling of KSHV LANA positioning on the host genome and examination of gene expression from promoters bound by KSHV LANA.
Contributor(s) Mercier A, Arias C, Madrid AS, Holdorf MM, Ganem D
Citation(s) 24696474
Submission date Mar 24, 2014
Last update date May 15, 2019
Street address 5300 CHIRON WAY
State/province CA
ZIP/Postal code 94608
Country USA
Platforms (2)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (33)
GSM1359483 ChIPseq_LANA_iSLK_rep1
GSM1359484 ChIPseq_LANA_iSLK219_rep1
GSM1359485 ChIPseq_LANA_iSLK219_dox_rep1
BioProject PRJNA242969
SRA SRP040694

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Supplementary file Size Download File type/resource
GSE56144_RAW.tar 250.0 Mb (http)(custom) TAR (of BED, GTF, TXT)
GSE56144_RNAseq_gene_diff.txt.gz 1.1 Mb (ftp)(http) TXT
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

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