Polycomb repressive complex 2 facilitates the nuclear export of the influenza viral genome through the interaction with M1

Asaka, Mitsuhiro; Kawaguchi, Akiko; Sakai, Yoshiko; Mori, Kotaro; Nagata, Kyosuke

doi:10.1038/srep33608

Cited by 8 publications

(9 citation statements)

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“…To make 3 9 FLAG-tagged CTCF WT expression vector, CTCF cDNA fragment from pBS-FLAG-CTCF [12] was cloned into pCAGGS-3 9 FLAG [13]. To construct 4A, T518A, 7A, 8A, and 8D expression vectors, cDNA fragments containing each point mutation were amplified by PCR using the primers shown in Table 1.…”

Section: Construction Of Plasmidsmentioning

confidence: 99%

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

et al. 2017

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During mitosis, higher order chromatin structures are disrupted and chromosomes are condensed to achieve accurate chromosome segregation. CCCTC‐binding factor (CTCF) is a highly conserved and ubiquitously expressed C2H2‐type zinc finger protein which is considered to be involved in epigenetic memory through regulation of higher order chromatin architecture. However, the regulatory mechanism of CTCF in mitosis is still unclear. Here we found that the DNA‐binding activity of CTCF is regulated in a phosphorylation‐dependent manner during mitosis. The linker domains of the CTCF zinc finger domain were found to be phosphorylated during mitosis. The phosphorylation of linker domains impaired the DNA‐binding activity in vitro. Mutation analyses showed that amino acid residues (Thr289, Thr317, Thr346, Thr374, Ser402, Ser461, and Thr518) located in the linker domains were phosphorylated during mitosis. Based on these results, we propose that the mitotic phosphorylation of the linker domains of CTCF is important for the dissociation of CTCF from mitotic chromatin.

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Section: Construction Of Plasmidsmentioning

confidence: 99%

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

et al. 2017

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“…Polycomb repressive complexes (PRCs) are crucial cellular regulators and are therefore modulated by a multitude of viruses for both productive as well as latent infections (8,(38)(39)(40)(41). In this study, we dissected the role of the two main complexes formed by polycomb group proteins, PRC1 and PRC2, during lytic HCMV replication.…”

Section: Discussionmentioning

confidence: 99%

A Noncanonical Function of Polycomb Repressive Complexes Promotes Human Cytomegalovirus Lytic DNA Replication and Serves as a Novel Cellular Target for Antiviral Intervention

Svrlanska

Reichel²,

Schilling³

et al. 2019

J Virol

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Chromatin-based modifications of herpesviral genomes play a crucial role in dictating the outcome of infection. Consistent with this, host cell multiprotein complexes, such as polycomb repressive complexes (PRCs), were proposed to act as epigenetic regulators of herpesviral latency. In particular, PRC2 has recently been shown to contribute to the silencing of human cytomegalovirus (HCMV) genomes. Here, we identify a novel proviral role of PRC1 and PRC2, the two main polycomb repressive complexes, during productive HCMV infection. Western blot analyses revealed strong HCMV-mediated upregulation of RING finger protein 1B (RING1B) and B lymphoma Moloney murine leukemia virus insertion region 1 homolog (BMI1) as well as of enhancer of zeste homolog 2 (EZH2), suppressor of zeste 12 (SUZ12), and embryonic ectoderm development (EED), which constitute the core components of PRC1 and PRC2, respectively. Furthermore, we observed a relocalization of PRC components to viral replication compartments, whereas histone modifications conferred by the respective PRCs were specifically excluded from these sites. Depletion of individual PRC1/PRC2 proteins by RNA interference resulted in a significant reduction of newly synthesized viral genomes and, in consequence, a decreased release of viral particles. Furthermore, accelerated native isolation of protein on nascent DNA (aniPOND) revealed a physical association of EZH2 and BMI1 with nascent HCMV DNA, suggesting a direct contribution of PRC proteins to viral DNA replication. Strikingly, substances solely inhibiting the enzymatic activity of PRC1/2 did not exert antiviral effects, while drugs affecting the abundance of PRC core components strongly compromised HCMV genome synthesis and particle release. Taken together, our data reveal an enzymatically independent, noncanonical function of both PRC1 and PRC2 during HCMV DNA replication, which may serve as a novel cellular target for antiviral therapy. IMPORTANCE Polycomb group (PcG) proteins are primarily known as transcriptional repressors that modify chromatin and contribute to the establishment and maintenance of cell fates. Furthermore, emerging evidence indicates that overexpression of PcG proteins in various types of cancers contributes to the dysregulation of cellular proliferation. Consequently, several inhibitors targeting PcG proteins are presently undergoing preclinical and clinical evaluation. Here, we show that infection with human cytomegalovirus also induces a strong upregulation of several PcG proteins. Our data suggest that viral DNA replication depends on a noncanonical function of polycomb repressor complexes which is independent of the so-far-described enzymatic activities of individual PcG factors. Importantly, we observe that a subclass of inhibitory drugs that affect the abundance of PcG proteins strongly interferes with viral replication. This principle may serve as a novel promising target for antiviral treatment. Citation Svrlanska A, Reichel A, Schilling E-M, Scherer M, Stamminger T, Reuter N. 2019. A noncano...

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“…vRNP in the nucleus of host cell interacts with heterochromatin marked with showed a decrease of virions progeny compared to wild type, but the replication and expression of viral RNA were not affected. It has been assumed that PRC2 complex recruits M1 onto vRNP, promoting the nuclear export of vRNP with a mechanism independent by methyltransferase activity of EZH2 (Asaka et al, 2017).…”

Section: Ezh2 In Viral Infectionsmentioning

confidence: 99%

“…Asaka, Kawaguchi, Sakai, Mori, and Nagata () showed the involvement of EZH2 in Influenza. Genome of influenza A is composed by eight‐segmented and single‐stranded RNAs (vRNA) organized in ribonucleoprotein complexes (vRNP) through the binding with nucleoprotein (NP) as shown in Figure a.…”

Section: Ezh2 In Viral Infectionsmentioning

confidence: 99%

“…EZH2 is considered a fascinating target for cancer diagnosis, prognosis and therapy and various studies are uncovering its role in virology. Asaka, Kawaguchi, Sakai, Mori, and Nagata (2017) showed the involvement of EZH2 in Influenza. Genome of influenza A is composed by eight-segmented and single-stranded RNAs (vRNA) organized in ribonucleoprotein complexes (vRNP) through the binding with nucleoprotein (NP) as shown in Figure 2a.…”

Section: Ezh2 In Viral Infectionsmentioning

confidence: 99%

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The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma

Sanna

Marchesi

Melone

et al. 2018

Journal Cellular Physiology

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Nowadays, epigenetics covers a crucial role in different fields of science. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), is a big proponent of how epigenetic changes can affect the initiation and progression of several diseases. Through its catalytic activity, responsible for the tri-methylation of lysine 27 of the histone H3 (H3K27me3), EZH2 is a good target for both diagnosis and therapy of different pathologies. A large number of studies have demonstrated its crucial role in cancer initiation and progression. Nevertheless, only recently its function in virus diseases has been uncovered; therefore, EZH2 can be an important promoter of viral carcinogenesis. This review explores the role of EZH2 in viral epigenetics based on recent progress that demonstrated the role of this protein in virus environment. In particular, the review focuses on EZH2 behavior in Hepatitis B Virus, analyzing its role in the rise of Hepatocellular Carcinoma.

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Polycomb repressive complex 2 facilitates the nuclear export of the influenza viral genome through the interaction with M1

Cited by 8 publications

References 50 publications

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

A Noncanonical Function of Polycomb Repressive Complexes Promotes Human Cytomegalovirus Lytic DNA Replication and Serves as a Novel Cellular Target for Antiviral Intervention

The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma

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