|
| Status |
Public on Jun 25, 2022 |
| Title |
KSHV Topologically Associating Domains in Latent Chromatin and Regulation of Reactivation |
| Organisms |
Homo sapiens; Human gammaherpesvirus 8 |
| Experiment type |
Other
|
| Summary |
Eukaryotic genomes are structurally organized via the formation of multiple loops that create gene expression regulatory units called topologically associating domains (TADs). Here we revealed the KSHV TAD structure at 500 base pair resolution and constructed a 3D KSHV genomic structural model. The latent KSHV genome formed very similar TAD structures among three different naturally infected PEL cell lines. When KSHV reactivation was triggered, genomic loops within TADs were dramatically decreased, while contacts extending outside of TAD borders increased, leading to formation of a larger regulatory unit with a shift from repressive to active compartments (B to A). The 3D structural model proposes that the immediate-early promoter region is localized on the periphery of the 3D viral genome, while highly inducible non-coding RNA regions moved toward the inner space of the structure, resembling the coordination of a "bird cage" during reactivation. Finally, inhibition of the initial burst of lytic gene expression by stop codon insertion in the viral transactivator reduced genomic loops, while supplementing K-Rta expression in trans during establishment of latency attenuated the defect. Our studies suggest that the latent 3D genomic structural information is embedded in the lytic gene transcription program.
|
| |
|
| Overall design |
Capture Hi-C was utilized to analyze the fine details of the three-dimensional structure (chromatin loops, TADs) of the KSHV genome during latent infection and lytic reactivation in three human cell lines.
|
| |
|
| Contributor(s) |
Campbell M, Chantarasrivong C, Yanagihashi Y, Davis RR, Lyu Y, Nakano K, Tepper CG, Izumiya Y |
| Citation(s) |
35867573 |
| 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 |
Dec 22, 2020 |
| Last update date |
Sep 26, 2022 |
| Contact name |
Clifford G. Tepper |
| E-mail(s) |
cgtepper@ucdavis.edu
|
| 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) |
| GPL25719 |
Illumina HiSeq 4000 (Homo sapiens; Human gammaherpesvirus 8) |
|
| Samples (10)
|
|
| Relations |
| BioProject |
PRJNA687220 |
| SRA |
SRP298931 |
Less...
More...