SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes.
SUMO
antigenic variation
plant homeodomain
post-translational modification
variant surface glycoprotein
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 12 2019
05 12 2019
Historique:
received:
01
03
2019
revised:
22
09
2019
accepted:
26
09
2019
pubmed:
7
11
2019
medline:
22
5
2020
entrez:
7
11
2019
Statut:
ppublish
Résumé
SUMOylation is a post-translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)-transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage-specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream-specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.
Identifiants
pubmed: 31693280
doi: 10.15252/embr.201948029
pmc: PMC6893287
doi:
Substances chimiques
Glycoproteins
0
Protozoan Proteins
0
Transcription Factors
0
RNA Polymerase I
EC 2.7.7.6
Banques de données
SRA
['PRJNA562785']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e48029Subventions
Organisme : Wellcome Trust
ID : 203134/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WTI 204697/Z/16/Z
Pays : United Kingdom
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : RTI2018-098834-B-I00
Pays : International
Organisme : Argentinian National Agency for Promotion of Scientific and Technological Research
ID : PICT-2016-0465
Pays : International
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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