LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus associated with KS and two lymphoproliferative diseases. Recent studies characterized epigenetic modification of KSHV episomes during latency and determined that latency-associated genes are associated with H3K4me3 while most lyt...

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Autores principales:	Jianhong Hu, Yajie Yang, Peter C Turner, Vaibhav Jain, Lauren M McIntyre, Rolf Renne
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/745d493209034533815f33e7c8622a8d
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spelling	oai:doaj.org-article:745d493209034533815f33e7c8622a8d2021-11-25T05:46:15ZLANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.1553-73661553-737410.1371/journal.ppat.1004240https://doaj.org/article/745d493209034533815f33e7c8622a8d2014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25033463/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus associated with KS and two lymphoproliferative diseases. Recent studies characterized epigenetic modification of KSHV episomes during latency and determined that latency-associated genes are associated with H3K4me3 while most lytic genes are associated with the silencing mark H3K27me3. Since the latency-associated nuclear antigen (LANA) (i) is expressed very early after de novo infection, (ii) interacts with transcriptional regulators and chromatin remodelers, and (iii) regulates the LANA and RTA promoters, we hypothesized that LANA may contribute to the establishment of latency through epigenetic control. We performed a detailed ChIP-seq analysis in cells of lymphoid and endothelial origin and compared H3K4me3, H3K27me3, polII, and LANA occupancy. On viral episomes LANA binding was detected at numerous lytic and latent promoters, which were transactivated by LANA using reporter assays. LANA binding was highly enriched at H3K4me3 peaks and this co-occupancy was also detected on many host gene promoters. Bioinformatic analysis of enriched LANA binding sites in combination with biochemical binding studies revealed three distinct binding patterns. A small subset of LANA binding sites showed sequence homology to the characterized LBS1/2 sequence in the viral terminal repeat. A large number of sites contained a novel LANA binding motif (TCCAT)3 which was confirmed by gel shift analysis. Third, some viral and cellular promoters did not contain LANA binding sites and are likely enriched through protein/protein interaction. LANA was associated with H3K4me3 marks and in PEL cells 86% of all LANA bound promoters were transcriptionally active, leading to the hypothesis that LANA interacts with the machinery that methylates H3K4. Co-immunoprecipitation demonstrated LANA association with endogenous hSET1 complexes in both lymphoid and endothelial cells suggesting that LANA may contribute to the epigenetic profile of KSHV episomes.Jianhong HuYajie YangPeter C TurnerVaibhav JainLauren M McIntyreRolf RennePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 7, p e1004240 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jianhong Hu Yajie Yang Peter C Turner Vaibhav Jain Lauren M McIntyre Rolf Renne LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
description	Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus associated with KS and two lymphoproliferative diseases. Recent studies characterized epigenetic modification of KSHV episomes during latency and determined that latency-associated genes are associated with H3K4me3 while most lytic genes are associated with the silencing mark H3K27me3. Since the latency-associated nuclear antigen (LANA) (i) is expressed very early after de novo infection, (ii) interacts with transcriptional regulators and chromatin remodelers, and (iii) regulates the LANA and RTA promoters, we hypothesized that LANA may contribute to the establishment of latency through epigenetic control. We performed a detailed ChIP-seq analysis in cells of lymphoid and endothelial origin and compared H3K4me3, H3K27me3, polII, and LANA occupancy. On viral episomes LANA binding was detected at numerous lytic and latent promoters, which were transactivated by LANA using reporter assays. LANA binding was highly enriched at H3K4me3 peaks and this co-occupancy was also detected on many host gene promoters. Bioinformatic analysis of enriched LANA binding sites in combination with biochemical binding studies revealed three distinct binding patterns. A small subset of LANA binding sites showed sequence homology to the characterized LBS1/2 sequence in the viral terminal repeat. A large number of sites contained a novel LANA binding motif (TCCAT)3 which was confirmed by gel shift analysis. Third, some viral and cellular promoters did not contain LANA binding sites and are likely enriched through protein/protein interaction. LANA was associated with H3K4me3 marks and in PEL cells 86% of all LANA bound promoters were transcriptionally active, leading to the hypothesis that LANA interacts with the machinery that methylates H3K4. Co-immunoprecipitation demonstrated LANA association with endogenous hSET1 complexes in both lymphoid and endothelial cells suggesting that LANA may contribute to the epigenetic profile of KSHV episomes.
format	article
author	Jianhong Hu Yajie Yang Peter C Turner Vaibhav Jain Lauren M McIntyre Rolf Renne
author_facet	Jianhong Hu Yajie Yang Peter C Turner Vaibhav Jain Lauren M McIntyre Rolf Renne
author_sort	Jianhong Hu
title	LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
title_short	LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
title_full	LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
title_fullStr	LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
title_full_unstemmed	LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
title_sort	lana binds to multiple active viral and cellular promoters and associates with the h3k4methyltransferase hset1 complex.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/745d493209034533815f33e7c8622a8d
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LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.

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