MLL1 is regulated by KSHV LANA and is important for virus latency
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.14/36462 |
Resumo: | Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-A crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors. |
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MLL1 is regulated by KSHV LANA and is important for virus latencyMixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-A crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors.Veritati - Repositório Institucional da Universidade Católica PortuguesaTan, MinLi, ShijunJuillard, FrancelineChitas, RuteCustódio, Tânia F.Xue, HanSzymula, AgnieszkaSun, QimingLiu, BingÁlvarez, Ángel L.Chen, SheSimas, J. PedroMcVey, Colin E.Kaye, Kenneth M.2022-01-14T11:42:34Z2021-12-162021-12-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/36462eng0305-104810.1093/nar/gkab109485122843132PMC868276434850113000736046000026info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-05T01:37:38Zoai:repositorio.ucp.pt:10400.14/36462Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:29:38.367761Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
MLL1 is regulated by KSHV LANA and is important for virus latency |
title |
MLL1 is regulated by KSHV LANA and is important for virus latency |
spellingShingle |
MLL1 is regulated by KSHV LANA and is important for virus latency Tan, Min |
title_short |
MLL1 is regulated by KSHV LANA and is important for virus latency |
title_full |
MLL1 is regulated by KSHV LANA and is important for virus latency |
title_fullStr |
MLL1 is regulated by KSHV LANA and is important for virus latency |
title_full_unstemmed |
MLL1 is regulated by KSHV LANA and is important for virus latency |
title_sort |
MLL1 is regulated by KSHV LANA and is important for virus latency |
author |
Tan, Min |
author_facet |
Tan, Min Li, Shijun Juillard, Franceline Chitas, Rute Custódio, Tânia F. Xue, Han Szymula, Agnieszka Sun, Qiming Liu, Bing Álvarez, Ángel L. Chen, She Simas, J. Pedro McVey, Colin E. Kaye, Kenneth M. |
author_role |
author |
author2 |
Li, Shijun Juillard, Franceline Chitas, Rute Custódio, Tânia F. Xue, Han Szymula, Agnieszka Sun, Qiming Liu, Bing Álvarez, Ángel L. Chen, She Simas, J. Pedro McVey, Colin E. Kaye, Kenneth M. |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Veritati - Repositório Institucional da Universidade Católica Portuguesa |
dc.contributor.author.fl_str_mv |
Tan, Min Li, Shijun Juillard, Franceline Chitas, Rute Custódio, Tânia F. Xue, Han Szymula, Agnieszka Sun, Qiming Liu, Bing Álvarez, Ángel L. Chen, She Simas, J. Pedro McVey, Colin E. Kaye, Kenneth M. |
description |
Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-A crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-12-16 2021-12-16T00:00:00Z 2022-01-14T11:42:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.14/36462 |
url |
http://hdl.handle.net/10400.14/36462 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0305-1048 10.1093/nar/gkab1094 85122843132 PMC8682764 34850113 000736046000026 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132016860463104 |