Accession	GSE147063
Status	2020/3/17
Title	Global epigenomic analysis of primary effusion lymphoma identifies MYC super-enhancers and enhancer RNAs associated with KSHV infection
Organism	Homo sapiens
Experiment type	Other;Genome binding/occupancy profiling by high throughput sequencing
Summary	Enhancers play indispensable roles in cell proliferation and survival through spatiotemporally regulating gene transcription. In addition, active enhancers and super-enhancers often produce noncoding enhancer RNAs (eRNAs) that precisely control RNA polymerase II activity. Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncogenic gamma-2 herpesvirus that causes Kaposi’s sarcoma and lymphoproliferative diseases of B-cell origin such as primary effusion lymphoma (PEL). It is well characterized that KSHV utilizes host epigenetic and nuclear machineries to control the switch between two life cycles, latency and lytic replication. However, how KSHV impacts the host epigenome at different stages of viral life cycle is not well understood. Using the analysis of global run-on sequencing (GRO-seq) and chromatin-immunoprecipitation sequencing (ChIP-seq), we profiled the dynamics of host transcriptional regulatory elements during latency and lytic replication of KSHV-infected PEL cells. This study showed that a number of critical host genes for KSHV latency, including MYC proto-oncogene, were under the control of super-enhancers and eRNAs that were globally repressed upon viral reactivation. A combination of circular chromosome conformation capture combined with sequencing (4C-seq), GRO-seq and ChIP-seq indicated that the eRNA-expressing super-enhance regions were located at downstream of the MYC gene in KSHV-infected PELs. Treatment of an epigenetic drug to block enhancer function or shRNA-mediated depletion of the eRNA expression significantly reduced MYC mRNA expression in KSHV-infected PELs. Finally, while cellular IRF4 acted upon the eRNAs and super-enhancers for MYC expression during latency, the KSHV viral IRF4 repressed cellular IRF4 expression upon reactivation, decreasing MYC expression and thereby, facilitating lytic replication. Taken together, these data suggest that KSHV acts as an epigenetic driver that modifies host epigenomic status by effectively regulating enhancer function upon reactivation.
Samples	GSM ID Sample info Characteristics Description GSM4413999 Latent_MYCpromoter_4Cseq cell line:TRExBCBL1-RTA; infection:KSHV; replication:Latent - GSM4414000 Latent_MYCenhancer_4Cseq cell line:TRExBCBL1-RTA; infection:KSHV; replication:Latent - GSM4414001 Latent_H3K27ac_ChIPseq-set1 cell line:TRExBCBL1-RTA; infection:KSHV; replication:Latent; chip antibody:rabbit anti-H3K27ac (Active Motif 39133 lot# 28518012) - GSM4414002 Lytic_H3K27ac_ChIPseq-set1 cell line:TRExBCBL1-RTA; infection:KSHV; replication:Lytic; chip antibody:rabbit anti-H3K27ac (Active Motif 39133 lot# 28518012) - GSM4414003 Latent_H3K27ac_ChIPseq-set2 cell line:TRExBCBL1-RTA; infection:KSHV; replication:Latent; chip antibody:rabbit anti-H3K27ac (Active Motif 39133 lot# 28518012) - GSM4414004 Lytic_H3K27ac_ChIPseq-set2 cell line:TRExBCBL1-RTA; infection:KSHV; replication:Lytic; chip antibody:rabbit anti-H3K27ac (Active Motif 39133 lot# 28518012) - GSM4414005 Latent_H3K4me1_ChIPseq cell line:TRExBCBL1-RTA; infection:KSHV; replication:Latent; chip antibody:rabbit anti-H3K4me1 (Abcam 8895 lot# GR3283236-1) - GSM4414006 Lytic_H3K4me1_ChIPseq cell line:TRExBCBL1-RTA; infection:KSHV; replication:Lytic; chip antibody:rabbit anti-H3K4me1 (Abcam 8895 lot# GR3283236-1) - GSM4414007 Latent_GROseq cell line:TRExBCBL1-RTA; infection:KSHV; replication:Latent - GSM4414008 Lytic_GROseq cell line:TRExBCBL1-RTA; infection:KSHV; replication:Lytic -
Platform	GPL18573  GPL27467  : Illumina NextSeq 500 (Homo sapiens);Illumina Hiseq 2500 (Homo sapiens)
Literature
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