Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Beijing 100101, China.
Sci Rep. 2017 Jan 3;7:39861. doi: 10.1038/srep39861.
CTCF is 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. CTCF is 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 CTCF interacts 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. CTCF knockdown 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 CTD Ser2P modified RNA Pol II near CTCF peaks relative to the Ser5P form in the viral genome. Consistent with this, CTCF knockdown reduced the Ser2P but increased Ser5P modified forms of RNA Pol II on viral genes. These results suggest that CTCF promotes HSV-1 lytic transcription by facilitating the elongation of RNA Pol II and preventing silenced chromatin on the viral genome.
CTCF 是一种重要的染色质调节剂，参与包括核组织和转录在内的重要核过程。单纯疱疹病毒 1 型（HSV-1）是一种普遍存在的人类病原体，可进入人类上皮细胞和许多其他细胞类型进行有性感染。已知 CTCF 在潜伏和再激活期间结合 HSV-1 基因组中的几个位点，但尚未定义其功能。在这里，我们通过 ChIP-seq 报道 CTCF 在裂解感染期间与 HSV-1 DNA 广泛相互作用，其敲低导致病毒转录、病毒基因组拷贝数和病毒产量减少。CTCF 敲低导致 H3K9me3 和 H3K27me3 增加，以及 RNA pol II 在病毒基因上的占有率降低。重要的是，ChIP-seq 分析显示，在病毒基因组中，相对于 Ser5P 形式，CTCF 峰附近的 CTD Ser2P 修饰的 RNA Pol II 水平更高。与此一致的是，CTCF 敲低减少了病毒基因上 Ser2P 修饰的 RNA Pol II，但增加了 Ser5P 修饰的 RNA Pol II。这些结果表明，CTCF 通过促进 RNA pol II 的延伸并防止病毒基因组上的沉默染色质，促进 HSV-1 裂解转录。
