Epigenetic Regulation of Kaposi's Sarcoma-Associated Herpesvirus Latency.

Mel Campbell,Wayne W Yeh,Pei-Ching Chang,Chen-Hsuan Kao,Wan-Shan Yang

doi:10.3389/fmicb.2020.00850

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus that infects humans and exhibits a biphasic life cycle consisting of latent and lytic phases. Following entry into host cells, the KSHV genome undergoes circularization and chromatinization into an extrachromosomal episome ultimately leading to the establishment of latency. The KSHV episome is organized into distinct chromatin domains marked by variations in repressive or activating epigenetic modifications, including DNA methylation, histone methylation, and histone acetylation. Thus, the development of KSHV latency is believed to be governed by epigenetic regulation. In the past decade, interrogation of the KSHV epitome by genome-wide approaches has revealed a complex epigenetic mark landscape across KSHV genome and has uncovered the important regulatory roles of epigenetic modifications in governing the development of KSHV latency. Here, we highlight many of the findings regarding the role of DNA methylation, histone modification, post-translational modification (PTM) of chromatin remodeling proteins, the contribution of long non-coding RNAs (lncRNAs) in regulating KSHV latency development, and the role of higher-order episomal chromatin architecture in the maintenance of latency and the latent-to-lytic switch.

Highlights

Reviewed by: Keiji Ueda, Osaka University, Japan Subhash C
We highlight many of the findings regarding the role of DNA methylation, histone modification, post-translational modification (PTM) of chromatin remodeling proteins, the contribution of long non-coding RNAs in regulating Kaposi’s sarcoma-associated herpesvirus (KSHV) latency development, and the role of higher-order episomal chromatin architecture in the maintenance of latency and the latent-to-lytic switch
Since KSHV latency-associated nuclear antigen (LANA) participates in the maintenance of latency through targeting KSHV K-Rta (Lu et al, 2006), after LANA is expressed, methylation of LANA by protein arginine methyltransferase 1 (PRMT1) may help stabilize LANA on the KSHV genomes (Figure 1Civ; Campbell et al, 2012), which recruit Polycomb repressive complex 2 (PRC2) (Toth et al, 2016) and hSET1 (Hu J. et al, 2014) onto the KSHV genomes and mediate the increase of the repressive mark H3K27me3 and the active mark H3K4me3, respectively

Summary

Introduction

Reviewed by: Keiji Ueda, Osaka University, Japan Subhash C. We highlight many of the findings regarding the role of DNA methylation, histone modification, post-translational modification (PTM) of chromatin remodeling proteins, the contribution of long non-coding RNAs (lncRNAs) in regulating KSHV latency development, and the role of higher-order episomal chromatin architecture in the maintenance of latency and the latent-to-lytic switch.

Results

Conclusion