SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes.

Abstract:

: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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Saura A,Iribarren PA,Rojas-Barros D,Bart JM,López-Farfán D,Andrés-León E,Vidal-Cobo I,Boehm C,Alvarez VE,Field MC,Navarro M

doi

10.15252/embr.201948029

subject

Has Abstract

pub_date

2019-12-05 00:00:00

pages

e48029

issue

12

eissn

1469-221X

issn

1469-3178

journal_volume

20

pub_type

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