Cell Cycle Control of Kaposi's Sarcoma-Associated Herpesvirus Latency Transcription by CTCF-Cohesin Interactions
- 15 June 2009
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 83 (12), 6199-6210
- https://doi.org/10.1128/jvi.00052-09
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) latency is characterized by the highly regulated transcription of a few viral genes essential for genome maintenance and host cell survival. A major latency control region has been identified upstream of the divergent promoters for the multicistronic transcripts encoding LANA (ORF73), vCyclin (ORF72), and vFLIP (ORF71) and for the complementary strand transcript encoding K14 and vGPCR (ORF74). Previous studies have shown that this major latency control region is occupied by the cellular chromatin boundary factor CTCF and chromosome structural maintenance proteins SMC1, SMC3, and RAD21, which comprise the cohesin complex. Deletion of the CTCF-cohesin binding site caused an inhibition of cell growth and viral genome instability. We now show that the KSHV genes regulated by CTCF-cohesin are under cell cycle control and that mutation of the CTCF binding sites abolished cell cycle-regulated transcription. Cohesin subunits assembled at the CTCF binding sites and bound CTCF proteins in a cell cycle-dependent manner. Subcellular distribution of CTCF and colocalization with cohesins also varied across the cell cycle. Ectopic expression of Rad21 repressed CTCF-regulated transcription of KSHV lytic genes, and a Rad21-CTCF chimeric protein converted CTCF into an efficient transcriptional repressor of KSHV genes normally activated in the G 2 phase. We conclude that cohesins interact with CTCF in mid-S phase and repress CTCF-regulated genes in a cell cycle-dependent manner. We propose that the CTCF-cohesin complex plays a critical role in regulating the cell cycle control of viral gene expression during latency and that failure to maintain cell cycle control of latent transcripts inhibits host cell proliferation and survival.Keywords
This publication has 51 references indexed in Scilit:
- CTCF regulates cell cycle progression of αβ T cells in the thymusThe EMBO Journal, 2008
- The LPS-Induced Transcriptional Upregulation of the Chicken Lysozyme Locus Involves CTCF Eviction and Noncoding RNA TranscriptionMolecular Cell, 2008
- Cohesins localize with CTCF at the KSHV latency control region and at cellular c-myc and H19/Igf2 insulatorsThe EMBO Journal, 2008
- We gather together: insulators and genome organizationCurrent Opinion in Genetics & Development, 2007
- High-Resolution Profiling of Histone Methylations in the Human GenomeCell, 2007
- Cohesin regulation: fashionable ways to wear a ringChromosoma, 2007
- Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C)Nature Genetics, 2006
- CTCF mediates long-range chromatin looping and local histone modification in the β-globin locusGenes & Development, 2006
- Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromesChromosoma, 2006
- Regulation of Epstein-Barr Virus Latency Type by the Chromatin Boundary Factor CTCFJournal of Virology, 2006