Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection
The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the gene is differentially methylated in ce...
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| creator | Vargas-Ayala, Romina C Jay, Antonin Manara, Francesca Maroui, Mohamed Ali Hernandez-Vargas, Hector Diederichs, Audrey Robitaille, Alexis Sirand, Cecilia Ceraolo, Maria Grazia Romero-Medina, Maria Carmen Cros, Marie Pierre Cuenin, Cyrille Durand, Geoffroy Le Calvez-Kelm, Florence Mundo, Lucia Leoncini, Lorenzo Manet, Evelyne Herceg, Zdenko Gruffat, Henri Accardi, Rosita |
| description | The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the
gene is differentially methylated in cell lines derived from Epstein-Barr virus (EBV)-associated endemic Burkitt lymphoma (eBL) compared with that in EBV-negative sporadic Burkitt lymphoma-derived cells. However, whether KDM2B plays a role in eBL development has not been previously investigated. Oncogenic viruses have been shown to hijack the host cell epigenome to complete their life cycle and to promote the transformation process by perturbing cell chromatin organization. Here, we investigated whether EBV alters KDM2B levels to enable its life cycle and promote B-cell transformation. We show that infection of B cells with EBV leads to downregulation of KDM2B levels. We also show that LMP1, one of the main EBV transforming proteins, induces increased DNMT1 recruitment to the
gene and augments its methylation. By altering KDM2B levels and performing chromatin immunoprecipitation in EBV-infected B cells, we show that KDM2B is recruited to the EBV gene promoters and inhibits their expression. Furthermore, forced KDM2B expression in immortalized B cells led to altered mRNA levels of some differentiation-related genes. Our data show that EBV deregulates KDM2B levels through an epigenetic mechanism and provide evidence for a role of KDM2B in regulating virus and host cell gene expression, warranting further investigations to assess the role of KDM2B in the process of EBV-mediated lymphomagenesis.
In Africa, Epstein-Barr virus infection is associated with endemic Burkitt lymphoma, a pediatric cancer. The molecular events leading to its development are poorly understood compared with those leading to sporadic Burkitt lymphoma. In a previous study, by analyzing the DNA methylation changes in endemic compared with sporadic Burkitt lymphoma cell lines, we identified several differential methylated genomic positions in the proximity of genes with a potential role in cancer, and among them was the
gene.
encodes a histone H3 demethylase already shown to be involved in some hematological disorders. However, whether KDM2B plays a role in the development of Epstein-Barr virus-mediated lymphoma has not been investigated before. In this study, we show that Epstein-Barr virus deregulates KDM2B expression and describe t |
| doi_str_mv | 10.1128/JVI.00273-19 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6580945</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2211325973</sourcerecordid><originalsourceid>FETCH-LOGICAL-c484t-3271453014f1087b3ec2b91c4e7aff76ea8ff9ed11c8130277a1d20aed69920e3</originalsourceid><addsrcrecordid>eNpdkU1vEzEQhi0EoiFw44x8bCW2eGzvhy9IbUlpIBIHoOJmOd7ZxrDxbm2naPvrcUmpgNNIM8-88_ES8hLYMQBv3ny4XB4zxmtRgHpEZsBUU5QlyMdkltO8KEXz7YA8i_E7YyBlJZ-SA8GUqpiqZ-TH0icMY28musb0E9HTtEG6GN0VekzO0oW_nbZIV1N0Hunhx6Pi84jWdbn0DreYNlNvIlJ-So1vc2NM6HxxakKgly7sIl36Dm1yg39OnnSmj_jiPs7J1_PFl7OLYvXp_fLsZFVY2chUCF6DLEVetgPW1GuBlq8VWIm16bq6QtN0ncIWwDYg8uW1gZYzg22lFGco5uTtXnfcrbfYWvQpmF6PwW1NmPRgnP634t1GXw03uiobpvLoOTnaC2z-a7s4Wem7XP6rZEzKG8js4f2wMFzvMCa9ddFi3xuPwy5qzgEEL1UtMvp6j9owxBiwe9AGpu-81NlL_dtLDSrjr_4-4wH-Y574BfUimbU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2211325973</pqid></control><display><type>article</type><title>Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Vargas-Ayala, Romina C ; Jay, Antonin ; Manara, Francesca ; Maroui, Mohamed Ali ; Hernandez-Vargas, Hector ; Diederichs, Audrey ; Robitaille, Alexis ; Sirand, Cecilia ; Ceraolo, Maria Grazia ; Romero-Medina, Maria Carmen ; Cros, Marie Pierre ; Cuenin, Cyrille ; Durand, Geoffroy ; Le Calvez-Kelm, Florence ; Mundo, Lucia ; Leoncini, Lorenzo ; Manet, Evelyne ; Herceg, Zdenko ; Gruffat, Henri ; Accardi, Rosita</creator><creatorcontrib>Vargas-Ayala, Romina C ; Jay, Antonin ; Manara, Francesca ; Maroui, Mohamed Ali ; Hernandez-Vargas, Hector ; Diederichs, Audrey ; Robitaille, Alexis ; Sirand, Cecilia ; Ceraolo, Maria Grazia ; Romero-Medina, Maria Carmen ; Cros, Marie Pierre ; Cuenin, Cyrille ; Durand, Geoffroy ; Le Calvez-Kelm, Florence ; Mundo, Lucia ; Leoncini, Lorenzo ; Manet, Evelyne ; Herceg, Zdenko ; Gruffat, Henri ; Accardi, Rosita</creatorcontrib><description>The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the
gene is differentially methylated in cell lines derived from Epstein-Barr virus (EBV)-associated endemic Burkitt lymphoma (eBL) compared with that in EBV-negative sporadic Burkitt lymphoma-derived cells. However, whether KDM2B plays a role in eBL development has not been previously investigated. Oncogenic viruses have been shown to hijack the host cell epigenome to complete their life cycle and to promote the transformation process by perturbing cell chromatin organization. Here, we investigated whether EBV alters KDM2B levels to enable its life cycle and promote B-cell transformation. We show that infection of B cells with EBV leads to downregulation of KDM2B levels. We also show that LMP1, one of the main EBV transforming proteins, induces increased DNMT1 recruitment to the
gene and augments its methylation. By altering KDM2B levels and performing chromatin immunoprecipitation in EBV-infected B cells, we show that KDM2B is recruited to the EBV gene promoters and inhibits their expression. Furthermore, forced KDM2B expression in immortalized B cells led to altered mRNA levels of some differentiation-related genes. Our data show that EBV deregulates KDM2B levels through an epigenetic mechanism and provide evidence for a role of KDM2B in regulating virus and host cell gene expression, warranting further investigations to assess the role of KDM2B in the process of EBV-mediated lymphomagenesis.
In Africa, Epstein-Barr virus infection is associated with endemic Burkitt lymphoma, a pediatric cancer. The molecular events leading to its development are poorly understood compared with those leading to sporadic Burkitt lymphoma. In a previous study, by analyzing the DNA methylation changes in endemic compared with sporadic Burkitt lymphoma cell lines, we identified several differential methylated genomic positions in the proximity of genes with a potential role in cancer, and among them was the
gene.
encodes a histone H3 demethylase already shown to be involved in some hematological disorders. However, whether KDM2B plays a role in the development of Epstein-Barr virus-mediated lymphoma has not been investigated before. In this study, we show that Epstein-Barr virus deregulates KDM2B expression and describe the underlying mechanisms. We also reveal a role of the demethylase in controlling viral and B-cell gene expression, thus highlighting a novel interaction between the virus and the cellular epigenome.</description><identifier>ISSN: 0022-538X</identifier><identifier>EISSN: 1098-5514</identifier><identifier>DOI: 10.1128/JVI.00273-19</identifier><identifier>PMID: 30996097</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Adolescent ; Adult ; B-Lymphocytes - virology ; Biochemistry, Molecular Biology ; Burkitt Lymphoma - metabolism ; Cancer ; Cell Line ; Child ; Child, Preschool ; Chromatin - metabolism ; Chromatin Immunoprecipitation ; DNA Methylation ; Down-Regulation ; Epigenesis, Genetic ; Epstein-Barr Virus Infections - genetics ; Epstein-Barr Virus Infections - metabolism ; F-Box Proteins - genetics ; F-Box Proteins - metabolism ; Female ; Gene Expression Regulation ; Herpesvirus 4, Human - physiology ; Human health and pathology ; Humans ; Infectious diseases ; Jumonji Domain-Containing Histone Demethylases - genetics ; Jumonji Domain-Containing Histone Demethylases - metabolism ; Life Sciences ; Male ; Microbiology and Parasitology ; Middle Aged ; Molecular biology ; Virology ; Virus-Cell Interactions ; Young Adult</subject><ispartof>Journal of virology, 2019-07, Vol.93 (13)</ispartof><rights>Copyright © 2019 American Society for Microbiology.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2019 American Society for Microbiology. 2019 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-3271453014f1087b3ec2b91c4e7aff76ea8ff9ed11c8130277a1d20aed69920e3</citedby><cites>FETCH-LOGICAL-c484t-3271453014f1087b3ec2b91c4e7aff76ea8ff9ed11c8130277a1d20aed69920e3</cites><orcidid>0000-0001-6045-2103 ; 0000-0002-9749-8276 ; 0000-0002-4735-6894 ; 0000-0001-7619-9982 ; 0000-0003-4109-3154</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580945/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580945/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30996097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02240044$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Vargas-Ayala, Romina C</creatorcontrib><creatorcontrib>Jay, Antonin</creatorcontrib><creatorcontrib>Manara, Francesca</creatorcontrib><creatorcontrib>Maroui, Mohamed Ali</creatorcontrib><creatorcontrib>Hernandez-Vargas, Hector</creatorcontrib><creatorcontrib>Diederichs, Audrey</creatorcontrib><creatorcontrib>Robitaille, Alexis</creatorcontrib><creatorcontrib>Sirand, Cecilia</creatorcontrib><creatorcontrib>Ceraolo, Maria Grazia</creatorcontrib><creatorcontrib>Romero-Medina, Maria Carmen</creatorcontrib><creatorcontrib>Cros, Marie Pierre</creatorcontrib><creatorcontrib>Cuenin, Cyrille</creatorcontrib><creatorcontrib>Durand, Geoffroy</creatorcontrib><creatorcontrib>Le Calvez-Kelm, Florence</creatorcontrib><creatorcontrib>Mundo, Lucia</creatorcontrib><creatorcontrib>Leoncini, Lorenzo</creatorcontrib><creatorcontrib>Manet, Evelyne</creatorcontrib><creatorcontrib>Herceg, Zdenko</creatorcontrib><creatorcontrib>Gruffat, Henri</creatorcontrib><creatorcontrib>Accardi, Rosita</creatorcontrib><title>Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection</title><title>Journal of virology</title><addtitle>J Virol</addtitle><description>The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the
gene is differentially methylated in cell lines derived from Epstein-Barr virus (EBV)-associated endemic Burkitt lymphoma (eBL) compared with that in EBV-negative sporadic Burkitt lymphoma-derived cells. However, whether KDM2B plays a role in eBL development has not been previously investigated. Oncogenic viruses have been shown to hijack the host cell epigenome to complete their life cycle and to promote the transformation process by perturbing cell chromatin organization. Here, we investigated whether EBV alters KDM2B levels to enable its life cycle and promote B-cell transformation. We show that infection of B cells with EBV leads to downregulation of KDM2B levels. We also show that LMP1, one of the main EBV transforming proteins, induces increased DNMT1 recruitment to the
gene and augments its methylation. By altering KDM2B levels and performing chromatin immunoprecipitation in EBV-infected B cells, we show that KDM2B is recruited to the EBV gene promoters and inhibits their expression. Furthermore, forced KDM2B expression in immortalized B cells led to altered mRNA levels of some differentiation-related genes. Our data show that EBV deregulates KDM2B levels through an epigenetic mechanism and provide evidence for a role of KDM2B in regulating virus and host cell gene expression, warranting further investigations to assess the role of KDM2B in the process of EBV-mediated lymphomagenesis.
In Africa, Epstein-Barr virus infection is associated with endemic Burkitt lymphoma, a pediatric cancer. The molecular events leading to its development are poorly understood compared with those leading to sporadic Burkitt lymphoma. In a previous study, by analyzing the DNA methylation changes in endemic compared with sporadic Burkitt lymphoma cell lines, we identified several differential methylated genomic positions in the proximity of genes with a potential role in cancer, and among them was the
gene.
encodes a histone H3 demethylase already shown to be involved in some hematological disorders. However, whether KDM2B plays a role in the development of Epstein-Barr virus-mediated lymphoma has not been investigated before. In this study, we show that Epstein-Barr virus deregulates KDM2B expression and describe the underlying mechanisms. We also reveal a role of the demethylase in controlling viral and B-cell gene expression, thus highlighting a novel interaction between the virus and the cellular epigenome.</description><subject>Adolescent</subject><subject>Adult</subject><subject>B-Lymphocytes - virology</subject><subject>Biochemistry, Molecular Biology</subject><subject>Burkitt Lymphoma - metabolism</subject><subject>Cancer</subject><subject>Cell Line</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromatin - metabolism</subject><subject>Chromatin Immunoprecipitation</subject><subject>DNA Methylation</subject><subject>Down-Regulation</subject><subject>Epigenesis, Genetic</subject><subject>Epstein-Barr Virus Infections - genetics</subject><subject>Epstein-Barr Virus Infections - metabolism</subject><subject>F-Box Proteins - genetics</subject><subject>F-Box Proteins - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Herpesvirus 4, Human - physiology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Jumonji Domain-Containing Histone Demethylases - genetics</subject><subject>Jumonji Domain-Containing Histone Demethylases - metabolism</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Microbiology and Parasitology</subject><subject>Middle Aged</subject><subject>Molecular biology</subject><subject>Virology</subject><subject>Virus-Cell Interactions</subject><subject>Young Adult</subject><issn>0022-538X</issn><issn>1098-5514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1vEzEQhi0EoiFw44x8bCW2eGzvhy9IbUlpIBIHoOJmOd7ZxrDxbm2naPvrcUmpgNNIM8-88_ES8hLYMQBv3ny4XB4zxmtRgHpEZsBUU5QlyMdkltO8KEXz7YA8i_E7YyBlJZ-SA8GUqpiqZ-TH0icMY28musb0E9HTtEG6GN0VekzO0oW_nbZIV1N0Hunhx6Pi84jWdbn0DreYNlNvIlJ-So1vc2NM6HxxakKgly7sIl36Dm1yg39OnnSmj_jiPs7J1_PFl7OLYvXp_fLsZFVY2chUCF6DLEVetgPW1GuBlq8VWIm16bq6QtN0ncIWwDYg8uW1gZYzg22lFGco5uTtXnfcrbfYWvQpmF6PwW1NmPRgnP634t1GXw03uiobpvLoOTnaC2z-a7s4Wem7XP6rZEzKG8js4f2wMFzvMCa9ddFi3xuPwy5qzgEEL1UtMvp6j9owxBiwe9AGpu-81NlL_dtLDSrjr_4-4wH-Y574BfUimbU</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Vargas-Ayala, Romina C</creator><creator>Jay, Antonin</creator><creator>Manara, Francesca</creator><creator>Maroui, Mohamed Ali</creator><creator>Hernandez-Vargas, Hector</creator><creator>Diederichs, Audrey</creator><creator>Robitaille, Alexis</creator><creator>Sirand, Cecilia</creator><creator>Ceraolo, Maria Grazia</creator><creator>Romero-Medina, Maria Carmen</creator><creator>Cros, Marie Pierre</creator><creator>Cuenin, Cyrille</creator><creator>Durand, Geoffroy</creator><creator>Le Calvez-Kelm, Florence</creator><creator>Mundo, Lucia</creator><creator>Leoncini, Lorenzo</creator><creator>Manet, Evelyne</creator><creator>Herceg, Zdenko</creator><creator>Gruffat, Henri</creator><creator>Accardi, Rosita</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6045-2103</orcidid><orcidid>https://orcid.org/0000-0002-9749-8276</orcidid><orcidid>https://orcid.org/0000-0002-4735-6894</orcidid><orcidid>https://orcid.org/0000-0001-7619-9982</orcidid><orcidid>https://orcid.org/0000-0003-4109-3154</orcidid></search><sort><creationdate>20190701</creationdate><title>Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection</title><author>Vargas-Ayala, Romina C ; Jay, Antonin ; Manara, Francesca ; Maroui, Mohamed Ali ; Hernandez-Vargas, Hector ; Diederichs, Audrey ; Robitaille, Alexis ; Sirand, Cecilia ; Ceraolo, Maria Grazia ; Romero-Medina, Maria Carmen ; Cros, Marie Pierre ; Cuenin, Cyrille ; Durand, Geoffroy ; Le Calvez-Kelm, Florence ; Mundo, Lucia ; Leoncini, Lorenzo ; Manet, Evelyne ; Herceg, Zdenko ; Gruffat, Henri ; Accardi, Rosita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-3271453014f1087b3ec2b91c4e7aff76ea8ff9ed11c8130277a1d20aed69920e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>B-Lymphocytes - virology</topic><topic>Biochemistry, Molecular Biology</topic><topic>Burkitt Lymphoma - metabolism</topic><topic>Cancer</topic><topic>Cell Line</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromatin - metabolism</topic><topic>Chromatin Immunoprecipitation</topic><topic>DNA Methylation</topic><topic>Down-Regulation</topic><topic>Epigenesis, Genetic</topic><topic>Epstein-Barr Virus Infections - genetics</topic><topic>Epstein-Barr Virus Infections - metabolism</topic><topic>F-Box Proteins - genetics</topic><topic>F-Box Proteins - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Herpesvirus 4, Human - physiology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Jumonji Domain-Containing Histone Demethylases - genetics</topic><topic>Jumonji Domain-Containing Histone Demethylases - metabolism</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Microbiology and Parasitology</topic><topic>Middle Aged</topic><topic>Molecular biology</topic><topic>Virology</topic><topic>Virus-Cell Interactions</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vargas-Ayala, Romina C</creatorcontrib><creatorcontrib>Jay, Antonin</creatorcontrib><creatorcontrib>Manara, Francesca</creatorcontrib><creatorcontrib>Maroui, Mohamed Ali</creatorcontrib><creatorcontrib>Hernandez-Vargas, Hector</creatorcontrib><creatorcontrib>Diederichs, Audrey</creatorcontrib><creatorcontrib>Robitaille, Alexis</creatorcontrib><creatorcontrib>Sirand, Cecilia</creatorcontrib><creatorcontrib>Ceraolo, Maria Grazia</creatorcontrib><creatorcontrib>Romero-Medina, Maria Carmen</creatorcontrib><creatorcontrib>Cros, Marie Pierre</creatorcontrib><creatorcontrib>Cuenin, Cyrille</creatorcontrib><creatorcontrib>Durand, Geoffroy</creatorcontrib><creatorcontrib>Le Calvez-Kelm, Florence</creatorcontrib><creatorcontrib>Mundo, Lucia</creatorcontrib><creatorcontrib>Leoncini, Lorenzo</creatorcontrib><creatorcontrib>Manet, Evelyne</creatorcontrib><creatorcontrib>Herceg, Zdenko</creatorcontrib><creatorcontrib>Gruffat, Henri</creatorcontrib><creatorcontrib>Accardi, Rosita</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vargas-Ayala, Romina C</au><au>Jay, Antonin</au><au>Manara, Francesca</au><au>Maroui, Mohamed Ali</au><au>Hernandez-Vargas, Hector</au><au>Diederichs, Audrey</au><au>Robitaille, Alexis</au><au>Sirand, Cecilia</au><au>Ceraolo, Maria Grazia</au><au>Romero-Medina, Maria Carmen</au><au>Cros, Marie Pierre</au><au>Cuenin, Cyrille</au><au>Durand, Geoffroy</au><au>Le Calvez-Kelm, Florence</au><au>Mundo, Lucia</au><au>Leoncini, Lorenzo</au><au>Manet, Evelyne</au><au>Herceg, Zdenko</au><au>Gruffat, Henri</au><au>Accardi, Rosita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection</atitle><jtitle>Journal of virology</jtitle><addtitle>J Virol</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>93</volume><issue>13</issue><issn>0022-538X</issn><eissn>1098-5514</eissn><abstract>The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the
gene is differentially methylated in cell lines derived from Epstein-Barr virus (EBV)-associated endemic Burkitt lymphoma (eBL) compared with that in EBV-negative sporadic Burkitt lymphoma-derived cells. However, whether KDM2B plays a role in eBL development has not been previously investigated. Oncogenic viruses have been shown to hijack the host cell epigenome to complete their life cycle and to promote the transformation process by perturbing cell chromatin organization. Here, we investigated whether EBV alters KDM2B levels to enable its life cycle and promote B-cell transformation. We show that infection of B cells with EBV leads to downregulation of KDM2B levels. We also show that LMP1, one of the main EBV transforming proteins, induces increased DNMT1 recruitment to the
gene and augments its methylation. By altering KDM2B levels and performing chromatin immunoprecipitation in EBV-infected B cells, we show that KDM2B is recruited to the EBV gene promoters and inhibits their expression. Furthermore, forced KDM2B expression in immortalized B cells led to altered mRNA levels of some differentiation-related genes. Our data show that EBV deregulates KDM2B levels through an epigenetic mechanism and provide evidence for a role of KDM2B in regulating virus and host cell gene expression, warranting further investigations to assess the role of KDM2B in the process of EBV-mediated lymphomagenesis.
In Africa, Epstein-Barr virus infection is associated with endemic Burkitt lymphoma, a pediatric cancer. The molecular events leading to its development are poorly understood compared with those leading to sporadic Burkitt lymphoma. In a previous study, by analyzing the DNA methylation changes in endemic compared with sporadic Burkitt lymphoma cell lines, we identified several differential methylated genomic positions in the proximity of genes with a potential role in cancer, and among them was the
gene.
encodes a histone H3 demethylase already shown to be involved in some hematological disorders. However, whether KDM2B plays a role in the development of Epstein-Barr virus-mediated lymphoma has not been investigated before. In this study, we show that Epstein-Barr virus deregulates KDM2B expression and describe the underlying mechanisms. We also reveal a role of the demethylase in controlling viral and B-cell gene expression, thus highlighting a novel interaction between the virus and the cellular epigenome.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>30996097</pmid><doi>10.1128/JVI.00273-19</doi><orcidid>https://orcid.org/0000-0001-6045-2103</orcidid><orcidid>https://orcid.org/0000-0002-9749-8276</orcidid><orcidid>https://orcid.org/0000-0002-4735-6894</orcidid><orcidid>https://orcid.org/0000-0001-7619-9982</orcidid><orcidid>https://orcid.org/0000-0003-4109-3154</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of virology, 2019-07, Vol.93 (13) |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Adult B-Lymphocytes - virology Biochemistry, Molecular Biology Burkitt Lymphoma - metabolism Cancer Cell Line Child Child, Preschool Chromatin - metabolism Chromatin Immunoprecipitation DNA Methylation Down-Regulation Epigenesis, Genetic Epstein-Barr Virus Infections - genetics Epstein-Barr Virus Infections - metabolism F-Box Proteins - genetics F-Box Proteins - metabolism Female Gene Expression Regulation Herpesvirus 4, Human - physiology Human health and pathology Humans Infectious diseases Jumonji Domain-Containing Histone Demethylases - genetics Jumonji Domain-Containing Histone Demethylases - metabolism Life Sciences Male Microbiology and Parasitology Middle Aged Molecular biology Virology Virus-Cell Interactions Young Adult |
| title | Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T01%3A42%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interplay%20between%20the%20Epigenetic%20Enzyme%20Lysine%20(K)-Specific%20Demethylase%202B%20and%20Epstein-Barr%20Virus%20Infection&rft.jtitle=Journal%20of%20virology&rft.au=Vargas-Ayala,%20Romina%20C&rft.date=2019-07-01&rft.volume=93&rft.issue=13&rft.issn=0022-538X&rft.eissn=1098-5514&rft_id=info:doi/10.1128/JVI.00273-19&rft_dat=%3Cproquest_pubme%3E2211325973%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2211325973&rft_id=info:pmid/30996097&rfr_iscdi=true |