SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

ANDREU SAURA; PAULA IRIBARREN; DOMINGO ROJAS-BARROS; JEAN M. BART; DIANA LÓPEZ-FARFÁN; EDUARDO ANDRÉS-LEÓN; ISABEL VIDAL-COBO; CORDULA BOEHM; VANINA ALVAREZ; MARK C. FIELD; MIGUEL NAVARRO

EMBO REPORTS

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2019

1469-221X

SUMO is a post-translational modification that positively regulates monoallelicexpression 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 suggests a role for SUMOylation. SNF2PH, a SUMOylated plant homeodomain (PH)-transcription factor is upregulated in the parasite bloodstreamform (BF). SNF2PH is enriched at the active VSG telomere and SUMOylation is a determinant for recruitment to the promoter. SNF2PH expression is required to maintain RNA polymerase at the VSG locus and thus VSG transcript levels. Further,ectopic overexpression of SNF2PH in insect forms, but not a mutant lacking the PH domain, induces expression of BF-specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription while the PH domain is required for BF developmental gene expression of surface proteins. These data suggest that SNF2PH functions as a positive activator, coupling infective form surface protein gene expression and VSG regulation, acting as a major controller of pathogenicity.