CTCF interacts with the lytic HSV-1 genome to promote viral transcription

CTCFis an essential chromatin regulator implicated in important nuclear processes including in nuclear organization and transcription. Herpes Simplex Virus-1 (HSV-1) is a ubiquitous human pathogen, which enters productive infection in human epithelial and many other cell types. CTCFis known to bind several sites in the HSV-1 genome during latency and reactivation, but its function has not been defined. Here, we report that CTCFinteracts extensively with the HSV-1 DNA during lytic infection by ChIP-seq, and its knockdown results in the reduction of viral transcription, viral genome copy number and virus yield. CTCFknockdown led to increased H3K9me3 and H3K27me3, and a reduction of RNA pol II occupancy on viral genes. Importantly, ChIP-seq analysis revealed that there is a higher level of CTDSer2P modified RNA Pol II near CTCFpeaks relative to the Ser5P form in the viral genome. Consistent with this, CTCFknockdown reduced the Ser2P but increased Ser5P modified forms of RNA Pol II on viral genes. These results suggest that CTCFpromotes HSV-1 lytic transcription by facilitating the elongation of RNA Pol II and preventing silenced chromatin on the viral genome.