|
| Status |
Public on Jan 01, 2014 |
| Title |
Biphasic euchromatin-to-heterochromatin transition on the KSHV genome following de novo infection |
| Platform organism |
Human herpesvirus 8 type M |
| Sample organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
|
| Summary |
The establishment of latency is an essential step for the life-long persistent infection and pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV). While the KSHV genome is chromatin-free in the virions, the viral DNA in latently infected cells has a chromatin structure that is characterized by a specific pattern of activating and repressive histone modifications that ultimately promote latent gene expression while suppressing lytic gene expression. To investigate the molecular events involved in the establishment of the latent chromatin structure during the pre-latency phase of KSHV infection, we performed a comprehensive epigenetic study to analyze the recruitment of chromatin regulatory factors onto the KSHV genome at various time-points following de novo infection of SLK and TIME cells. This showed that the KSHV genome undergoes a biphasic chromatinization following de novo infection. Initially, a transcriptionally active chromatin (euchromatin), characterized by high levels of the H3K4me3 and acetylated H3K27 (H3K27ac) activating histone marks, was deposited on the viral episome and was accompanied by the temporary induction of a limited number of lytic genes. Interestingly, transient expression of the RTA protein facilitated the increases of H3K4me3 and H3K27ac occupancy on the KSHV episome during de novo infection. Between 24-72 hours post-infection, as the levels of these activating histone marks declined on the KSHV genome, the levels of the repressive H3K27me3 and H2AK119ub histone marks increased concomitantly with the decline of lytic gene expression. Importantly, this transition to heterochromatin was dependent on both the Polycomb Repressive Complex 2 and 1. In contrast, upon infection of human gingiva-derived epithelial cells, the KSHV genome underwent a continuously transcription-active euchromatinization, resulting in efficient lytic gene expression. Our data demonstrate that the KSHV genome undergoes a temporally ordered biphasic euchromatin-to-heterochromatin transition in endothelial cells, leading to latent infection, whereas KSHV preferentially adopts a transcriptionally active euchromatin in oral epithelial cells, resulting in lytic gene expression. Our results suggest that the differential epigenetic modification of the KSHV genome in distinct cell types is a potential determining factor for latent infection vs. lytic replication of KSHV.
Please see above.
|
| |
|
| Overall design |
16 hybridizations: ChIP and Input DNA
|
| |
|
| Contributor(s) |
Toth Z, Jung JU |
| Citation(s) |
24367262 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P30 CA093373 |
Cancer Center Support Grant P30 |
UNIVERSITY OF CALIFORNIA DAVIS |
PRIMO N. LARA |
|
| |
| Submission date |
Oct 24, 2013 |
| Last update date |
Apr 18, 2014 |
| Contact name |
Clifford G. Tepper |
| E-mail(s) |
[email protected]
|
| Phone |
916-734-7195
|
| Organization name |
UC Davis School of Medicine
|
| Department |
Biochemistry and Molecular Medicine
|
| Street address |
4645 2nd Avenue, Room 2300A
|
| City |
Sacramento |
| State/province |
CA |
| ZIP/Postal code |
95817 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17838 |
Agilent-023116 Human herpesvirus U75698 |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA224552 |
Less...
More...