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| Status |
Public on Dec 16, 2015 |
| Title |
Identification of MEF2B, EBF1, and IL6R as chromosome bound targets of EBNA1 essential for EBV infected B-lymphocyte survival |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
EBNA1 is the EBV-encoded nuclear antigen required for viral episome maintenance during latency. EBNA1 is a sequence specific DNA binding protein with high affinity binding sites for the viral genome, especially OriP. EBNA1 can also bind sequence specifically to a large number of sites in the host cellular genome, but the function of these binding sites has remained elusive. EBNA1 is also known to provide a host cell survival function, but the molecular mechanisms accounting for this function are not completely understood. Here, we show by integrating ChIP-Seq and RNA-Seq with experimental validation that MEF2B, IL6R, and EBF1 are high confidence target genes of EBNA1 that are essential for viability of B-lymphocytes latently infected with EBV. We show that EBNA1 binds to ~1000 sites with many, but not all, universally bound in different cell types, including Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC). We find that a large subset of EBNA1 binding sites are located proximal to transcription start sites and correlate genome-wide with transcription activity. EBNA1 bound to genes of high significance for B-cell growth and function, including MEF2B, IL6R, EBF1, RNF145, POU2F1, KDM4C, FGR, EGFR, LAIR, CDC7, CD44, and IL17A. EBNA1 depletion from latently infected LCLs results in the loss of cell proliferation, and the loss of gene expression for some EBNA1-bound genes, including MEF2B, EBF1, and IL6R. Depletion of MEF2B, EBF1, or IL6R partially phenocopies EBNA1-depletion by decreasing EBV-positive cell growth and viability. These findings indicate that EBNA1 binds to a large cohort of cellular genes important for cell viability, and implicates EBNA1 as a master coordinator of host cell gene expression important for enhanced survival of latently infected cells.
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| Overall design |
Examination of EBNA1 binding in Raji, MutuI, LCL and C666-1 cells and EBNA1 knockdown effect on mRNA gene expression in LCL
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| Contributor(s) |
Lieberman PM, Tempera I |
| Citation(s) |
26468528 |
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| Submission date |
Oct 09, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
priyaw@wistar.org
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| Phone |
2154956837
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| Organization name |
The Wistar Institute
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| Department |
Bioinformatics
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| Lab |
Genomics
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| Street address |
3601 Spruce Street
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA298334 |
| SRA |
SRP064652 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE73887_C6661_EBNA1_vs_C6661_IgG.txt.gz |
195.3 Kb |
(ftp)(http) |
TXT |
| GSE73887_C6661_EBNA1_vs_LCL_EBNA1.txt.gz |
242.5 Kb |
(ftp)(http) |
TXT |
| GSE73887_C6661_EBNA1_vs_MUTU_EBNA1.txt.gz |
239.8 Kb |
(ftp)(http) |
TXT |
| GSE73887_C6661_EBNA1_vs_RAJI_EBNA1.txt.gz |
65.0 Kb |
(ftp)(http) |
TXT |
| GSE73887_C6661_EBNA1_vs_combine_IgG.txt.gz |
186.5 Kb |
(ftp)(http) |
TXT |
| GSE73887_C6661_EBNA1_vs_combine_IgG_3.txt.gz |
167.8 Kb |
(ftp)(http) |
TXT |
| GSE73887_GeneExpressionResults.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE73887_LCL_EBNA1_vs_C6661_EBNA1.txt.gz |
136.9 Kb |
(ftp)(http) |
TXT |
| GSE73887_LCL_EBNA1_vs_LCL_IgG.txt.gz |
312.1 Kb |
(ftp)(http) |
TXT |
| GSE73887_LCL_EBNA1_vs_MUTU_EBNA1.txt.gz |
328.1 Kb |
(ftp)(http) |
TXT |
| GSE73887_LCL_EBNA1_vs_RAJI_EBNA1.txt.gz |
20.3 Kb |
(ftp)(http) |
TXT |
| GSE73887_LCL_EBNA1_vs_combine_IgG.txt.gz |
280.6 Kb |
(ftp)(http) |
TXT |
| GSE73887_LCL_EBNA1_vs_combine_IgG_3.txt.gz |
299.9 Kb |
(ftp)(http) |
TXT |
| GSE73887_MUTU_EBNA1_vs_C6661_EBNA1.txt.gz |
74.7 Kb |
(ftp)(http) |
TXT |
| GSE73887_MUTU_EBNA1_vs_LCL_EBNA1.txt.gz |
111.3 Kb |
(ftp)(http) |
TXT |
| GSE73887_MUTU_EBNA1_vs_MUTU_IgG.txt.gz |
377.0 Kb |
(ftp)(http) |
TXT |
| GSE73887_MUTU_EBNA1_vs_RAJI_EBNA1.txt.gz |
23.7 Kb |
(ftp)(http) |
TXT |
| GSE73887_MUTU_EBNA1_vs_combine_IgG.txt.gz |
268.5 Kb |
(ftp)(http) |
TXT |
| GSE73887_MUTU_EBNA1_vs_combine_IgG_3.txt.gz |
265.2 Kb |
(ftp)(http) |
TXT |
| GSE73887_RAJI_EBNA1_vs_C6661_EBNA1.txt.gz |
140.0 Kb |
(ftp)(http) |
TXT |
| GSE73887_RAJI_EBNA1_vs_LCL_EBNA1.txt.gz |
155.3 Kb |
(ftp)(http) |
TXT |
| GSE73887_RAJI_EBNA1_vs_MUTU_EBNA1.txt.gz |
137.1 Kb |
(ftp)(http) |
TXT |
| GSE73887_RAJI_EBNA1_vs_RAJI_IgG.txt.gz |
25.7 Kb |
(ftp)(http) |
TXT |
| GSE73887_RAJI_EBNA1_vs_combine_IgG.txt.gz |
138.3 Kb |
(ftp)(http) |
TXT |
| GSE73887_RAJI_EBNA1_vs_combine_IgG_3.txt.gz |
138.1 Kb |
(ftp)(http) |
TXT |
| GSE73887_readme.txt |
3.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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