The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection

Research output: Contribution to journal › Journal article › Research › peer-review

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The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection. / Sourvinos, George; Morou, Antigoni; Sanidas, Ioannis; Codruta, Ignea; Ezell, Scott A; Doxaki, Christina; Kampranis, Sotirios; Kottakis, Filippos; Tsichlis, Philip N.

In: P L o S Pathogens, Vol. 10, No. 5, 2014, p. e1004136.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sourvinos, G, Morou, A, Sanidas, I, Codruta, I, Ezell, SA, Doxaki, C, Kampranis, S, Kottakis, F & Tsichlis, PN 2014, 'The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection', P L o S Pathogens, vol. 10, no. 5, pp. e1004136. https://doi.org/10.1371/journal.ppat.1004136

APA

Sourvinos, G., Morou, A., Sanidas, I., Codruta, I., Ezell, S. A., Doxaki, C., Kampranis, S., Kottakis, F., & Tsichlis, P. N. (2014). The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection. P L o S Pathogens, 10(5), e1004136. https://doi.org/10.1371/journal.ppat.1004136

Vancouver

Sourvinos G, Morou A, Sanidas I, Codruta I, Ezell SA, Doxaki C et al. The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection. P L o S Pathogens. 2014;10(5):e1004136. https://doi.org/10.1371/journal.ppat.1004136

Author

Sourvinos, George ; Morou, Antigoni ; Sanidas, Ioannis ; Codruta, Ignea ; Ezell, Scott A ; Doxaki, Christina ; Kampranis, Sotirios ; Kottakis, Filippos ; Tsichlis, Philip N. / The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection. In: P L o S Pathogens. 2014 ; Vol. 10, No. 5. pp. e1004136.

Bibtex

@article{6b4611986e924cfd8a4071a44cd62fa7,
title = "The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection",
abstract = "Earlier studies had suggested that epigenetic mechanisms play an important role in the control of human cytomegalovirus (HCMV) infection. Here we show that productive HCMV infection is indeed under the control of histone H3K27 trimethylation. The histone H3K27 methyltransferase EZH2, and its regulators JARID2 and NDY1/KDM2B repress GFI1, a transcriptional repressor of the major immediate-early promoter (MIEP) of HCMV. Knocking down EZH2, NDY1/KDM2B or JARID2 relieves the repression and results in the upregulation of GFI1. During infection, the incoming HCMV rapidly downregulates the GFI1 mRNA and protein in both wild-type cells and in cells in which EZH2, NDY1/KDM2B or JARID2 were knocked down. However, since the pre-infection levels of GFI1 in the latter cells are significantly higher, the virus fails to downregulate it to levels permissive for MIEP activation and viral infection. Following the EZH2-NDY1/KDM2B-JARID2-independent downregulation of GFI1 in the early stages of infection, the virus also initiates an EZH2-NDY1/ΚDM2Β-JARID2-dependent program that represses GFI1 throughout the infection cycle. The EZH2 knockdown also delays histone H3K27 trimethylation in the immediate early region of HCMV, which is accompanied by a drop in H3K4 trimethylation that may contribute to the shEZH2-mediated repression of the major immediate early HCMV promoter. These data show that HCMV uses multiple mechanisms to allow the activation of the HCMV MIEP and to prevent cellular mechanisms from blocking the HCMV replication program.",
keywords = "Antigens, Viral, Cells, Cultured, Cytomegalovirus, Cytomegalovirus Infections, DNA-Binding Proteins, Down-Regulation, F-Box Proteins, HEK293 Cells, HeLa Cells, Humans, Immediate-Early Proteins, Jumonji Domain-Containing Histone Demethylases, Polycomb Repressive Complex 2, Promoter Regions, Genetic, Signal Transduction, Transcription Factors, Viral Proteins, Virus Replication",
author = "George Sourvinos and Antigoni Morou and Ioannis Sanidas and Ignea Codruta and Ezell, {Scott A} and Christina Doxaki and Sotirios Kampranis and Filippos Kottakis and Tsichlis, {Philip N}",
year = "2014",
doi = "10.1371/journal.ppat.1004136",
language = "English",
volume = "10",
pages = "e1004136",
journal = "P L o S Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "5",

}

RIS

TY - JOUR

T1 - The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection

AU - Sourvinos, George

AU - Morou, Antigoni

AU - Sanidas, Ioannis

AU - Codruta, Ignea

AU - Ezell, Scott A

AU - Doxaki, Christina

AU - Kampranis, Sotirios

AU - Kottakis, Filippos

AU - Tsichlis, Philip N

PY - 2014

Y1 - 2014

N2 - Earlier studies had suggested that epigenetic mechanisms play an important role in the control of human cytomegalovirus (HCMV) infection. Here we show that productive HCMV infection is indeed under the control of histone H3K27 trimethylation. The histone H3K27 methyltransferase EZH2, and its regulators JARID2 and NDY1/KDM2B repress GFI1, a transcriptional repressor of the major immediate-early promoter (MIEP) of HCMV. Knocking down EZH2, NDY1/KDM2B or JARID2 relieves the repression and results in the upregulation of GFI1. During infection, the incoming HCMV rapidly downregulates the GFI1 mRNA and protein in both wild-type cells and in cells in which EZH2, NDY1/KDM2B or JARID2 were knocked down. However, since the pre-infection levels of GFI1 in the latter cells are significantly higher, the virus fails to downregulate it to levels permissive for MIEP activation and viral infection. Following the EZH2-NDY1/KDM2B-JARID2-independent downregulation of GFI1 in the early stages of infection, the virus also initiates an EZH2-NDY1/ΚDM2Β-JARID2-dependent program that represses GFI1 throughout the infection cycle. The EZH2 knockdown also delays histone H3K27 trimethylation in the immediate early region of HCMV, which is accompanied by a drop in H3K4 trimethylation that may contribute to the shEZH2-mediated repression of the major immediate early HCMV promoter. These data show that HCMV uses multiple mechanisms to allow the activation of the HCMV MIEP and to prevent cellular mechanisms from blocking the HCMV replication program.

AB - Earlier studies had suggested that epigenetic mechanisms play an important role in the control of human cytomegalovirus (HCMV) infection. Here we show that productive HCMV infection is indeed under the control of histone H3K27 trimethylation. The histone H3K27 methyltransferase EZH2, and its regulators JARID2 and NDY1/KDM2B repress GFI1, a transcriptional repressor of the major immediate-early promoter (MIEP) of HCMV. Knocking down EZH2, NDY1/KDM2B or JARID2 relieves the repression and results in the upregulation of GFI1. During infection, the incoming HCMV rapidly downregulates the GFI1 mRNA and protein in both wild-type cells and in cells in which EZH2, NDY1/KDM2B or JARID2 were knocked down. However, since the pre-infection levels of GFI1 in the latter cells are significantly higher, the virus fails to downregulate it to levels permissive for MIEP activation and viral infection. Following the EZH2-NDY1/KDM2B-JARID2-independent downregulation of GFI1 in the early stages of infection, the virus also initiates an EZH2-NDY1/ΚDM2Β-JARID2-dependent program that represses GFI1 throughout the infection cycle. The EZH2 knockdown also delays histone H3K27 trimethylation in the immediate early region of HCMV, which is accompanied by a drop in H3K4 trimethylation that may contribute to the shEZH2-mediated repression of the major immediate early HCMV promoter. These data show that HCMV uses multiple mechanisms to allow the activation of the HCMV MIEP and to prevent cellular mechanisms from blocking the HCMV replication program.

KW - Antigens, Viral

KW - Cells, Cultured

KW - Cytomegalovirus

KW - Cytomegalovirus Infections

KW - DNA-Binding Proteins

KW - Down-Regulation

KW - F-Box Proteins

KW - HEK293 Cells

KW - HeLa Cells

KW - Humans

KW - Immediate-Early Proteins

KW - Jumonji Domain-Containing Histone Demethylases

KW - Polycomb Repressive Complex 2

KW - Promoter Regions, Genetic

KW - Signal Transduction

KW - Transcription Factors

KW - Viral Proteins

KW - Virus Replication

U2 - 10.1371/journal.ppat.1004136

DO - 10.1371/journal.ppat.1004136

M3 - Journal article

C2 - 24830456

VL - 10

SP - e1004136

JO - P L o S Pathogens

JF - P L o S Pathogens

SN - 1553-7366

IS - 5

ER -

ID: 159084768