A histone methyltransferase modulates antigenic variation in African trypanosomes.

To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evas...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Luisa M Figueiredo, Christian J Janzen, George A M Cross
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a54360074b6e4c978542bf8e10e3199a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a54360074b6e4c978542bf8e10e3199a
record_format	dspace
spelling	oai:doaj.org-article:a54360074b6e4c978542bf8e10e3199a2021-11-25T05:33:17ZA histone methyltransferase modulates antigenic variation in African trypanosomes.1544-91731545-788510.1371/journal.pbio.0060161https://doaj.org/article/a54360074b6e4c978542bf8e10e3199a2008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18597556/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evasion relies on two important features: exposing a single type of VSG at the cell surface and periodically and very rapidly switching the expressed VSG. Transcriptional switching between resident telomeric VSG genes does not involve DNA rearrangements, and regulation is probably epigenetic. The histone methyltransferase DOT1B is a nonessential protein that trimethylates lysine 76 of histone H3 in Trypanosoma brucei. Here we report that transcriptionally silent telomeric VSGs become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected. DOT1B also is involved in the kinetics of VSG switching: in DeltaDOT1B cells, the transcriptional switch is so slow that cells expressing two VSGs persist for several weeks, indicating that monoallelic transcription is compromised. We conclude that DOT1B is required to maintain strict VSG silencing and to ensure rapid transcriptional VSG switching, demonstrating that epigenetics plays an important role in regulating antigenic variation in T. brucei.Luisa M FigueiredoChristian J JanzenGeorge A M CrossPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 6, Iss 7, p e161 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Luisa M Figueiredo Christian J Janzen George A M Cross A histone methyltransferase modulates antigenic variation in African trypanosomes.
description	To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evasion relies on two important features: exposing a single type of VSG at the cell surface and periodically and very rapidly switching the expressed VSG. Transcriptional switching between resident telomeric VSG genes does not involve DNA rearrangements, and regulation is probably epigenetic. The histone methyltransferase DOT1B is a nonessential protein that trimethylates lysine 76 of histone H3 in Trypanosoma brucei. Here we report that transcriptionally silent telomeric VSGs become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected. DOT1B also is involved in the kinetics of VSG switching: in DeltaDOT1B cells, the transcriptional switch is so slow that cells expressing two VSGs persist for several weeks, indicating that monoallelic transcription is compromised. We conclude that DOT1B is required to maintain strict VSG silencing and to ensure rapid transcriptional VSG switching, demonstrating that epigenetics plays an important role in regulating antigenic variation in T. brucei.
format	article
author	Luisa M Figueiredo Christian J Janzen George A M Cross
author_facet	Luisa M Figueiredo Christian J Janzen George A M Cross
author_sort	Luisa M Figueiredo
title	A histone methyltransferase modulates antigenic variation in African trypanosomes.
title_short	A histone methyltransferase modulates antigenic variation in African trypanosomes.
title_full	A histone methyltransferase modulates antigenic variation in African trypanosomes.
title_fullStr	A histone methyltransferase modulates antigenic variation in African trypanosomes.
title_full_unstemmed	A histone methyltransferase modulates antigenic variation in African trypanosomes.
title_sort	histone methyltransferase modulates antigenic variation in african trypanosomes.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/a54360074b6e4c978542bf8e10e3199a
work_keys_str_mv	AT luisamfigueiredo ahistonemethyltransferasemodulatesantigenicvariationinafricantrypanosomes AT christianjjanzen ahistonemethyltransferasemodulatesantigenicvariationinafricantrypanosomes AT georgeamcross ahistonemethyltransferasemodulatesantigenicvariationinafricantrypanosomes AT luisamfigueiredo histonemethyltransferasemodulatesantigenicvariationinafricantrypanosomes AT christianjjanzen histonemethyltransferasemodulatesantigenicvariationinafricantrypanosomes AT georgeamcross histonemethyltransferasemodulatesantigenicvariationinafricantrypanosomes
_version_	1718414657272676352

A histone methyltransferase modulates antigenic variation in African trypanosomes.

Ejemplares similares