SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F19%3A00520462" target="_blank" >RIV/60077344:_____/19:00520462 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.embopress.org/doi/pdf/10.15252/embr.201948029" target="_blank" >https://www.embopress.org/doi/pdf/10.15252/embr.201948029</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15252/embr.201948029" target="_blank" >10.15252/embr.201948029</a>

Jazyk výsledku

angličtina

Název v původním jazyce

SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

EMBO REPORTS

ISSN

1469-3178

e-ISSN

—

Svazek periodika

NOV 2019

Číslo periodika v rámci svazku

NOV 2019

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

e48029

Kód UT WoS článku

000494626400001

EID výsledku v databázi Scopus

2-s2.0-85074820721