Understanding differential expression of genes during EBV lytic cycle reactivation by employing high throughput RNA-sequencing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA995436 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25302171.fastq.gz | Fastqsanger.gz | |||
| SRR25302172.fastq.gz | Fastqsanger.gz | |||
| SRR25302173.fastq.gz | Fastqsanger.gz | |||
| SRR25302174.fastq.gz | Fastqsanger.gz | |||
| SRR25302175.fastq.gz | Fastqsanger.gz |
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Project description:As a human tumor virus, EBV is present as a latent infection in its associated malignancies where genetic and epigenetic changes have been shown to impede cellular differentiation and viral reactivation. One such change is increased levels of the Wnt signaling effector, lymphoid enhancer binding factor 1 (LEF1) following EBV epithelial infection. In silico analysis of EBV type 1 and 2 genomes identified over 20 Wnt-response elements suggesting that LEF1 may directly bind the EBV genome and regulate the viral life cycle. Using CUT&RUN-seq, LEF1 was shown to bind the latent EBV genome at various sites encoding viral lytic products that included the immediate early transactivator BZLF1 and viral primase BSLF1 genes. SiRNA depletion of specific LEF1 isoforms revealed that the alternative-promoter derived isoform with an N-terminal truncation (∆N LEF1) transcriptionally repressed lytic genes associated with LEF1 binding. Furthermore, forced expression of the ∆N LEF1 isoform antagonized EBV reactivation from latency. The LEF1 mediated repression requires histone deacetylase activity through either recruitment or a direct intrinsic histone deacetylase activity. SiRNA depletion of LEF1 resulted in increased histone 3 lysine 9 and lysine 27 acetylation at LEF1 binding sites and across the EBV genome. These results support a novel role for LEF1 in maintaining EBV latency and restriction viral reactivation via repressive chromatin remodeling of critical lytic cycle factors
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