Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei

Povelones, M. L. , Gluenz, E. , Dembek, M. , Gull, K. and Rudenko, G. (2012) Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei. PLoS Pathogens, 8(11), e1003010. (doi: 10.1371/journal.ppat.1003010) (PMID:23133390) (PMCID:PMC3486875)

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Abstract

The African sleeping sickness parasite Trypanosoma brucei evades the host immune system through antigenic variation of its variant surface glycoprotein (VSG) coat. Although the T. brucei genome contains ∼1500 VSGs, only one VSG is expressed at a time from one of about 15 subtelomeric VSG expression sites (ESs). For antigenic variation to work, not only must the vast VSG repertoire be kept silent in a genome that is mainly constitutively transcribed, but the frequency of VSG switching must be strictly controlled. Recently it has become clear that chromatin plays a key role in silencing inactive ESs, thereby ensuring monoallelic expression of VSG. We investigated the role of the linker histone H1 in chromatin organization and ES regulation in T. brucei. T. brucei histone H1 proteins have a different domain structure to H1 proteins in higher eukaryotes. However, we show that they play a key role in the maintenance of higher order chromatin structure in bloodstream form T. brucei as visualised by electron microscopy. In addition, depletion of histone H1 results in chromatin becoming generally more accessible to endonucleases in bloodstream but not in insect form T. brucei. The effect on chromatin following H1 knock-down in bloodstream form T. brucei is particularly evident at transcriptionally silent ES promoters, leading to 6–8 fold derepression of these promoters. T. brucei histone H1 therefore appears to be important for the maintenance of repressed chromatin in bloodstream form T. brucei. In particular H1 plays a role in downregulating silent ESs, arguing that H1-mediated chromatin functions in antigenic variation in T. brucei.

Item Type:Articles
Additional Information:This research was funded by the Wellcome Trust. G.R. is a Wellcome Senior Fellow in the Basic Biomedical Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gluenz, Dr Eva
Authors: Povelones, M. L., Gluenz, E., Dembek, M., Gull, K., and Rudenko, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Published Online:01 November 2012
Copyright Holders:Copyright © 2012 Povelones et al.
First Published:First published in PLoS Pathogens 8(11):e1003010
Publisher Policy:Reproduced under a Creative Commons License

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