The role in SUMO chains in nuclear foci formation and chromatin organization in Trypanosoma brucei procyclic form

BERAZATEGUI, MA; IRIBARREN, PA; DI MARZIO, LA; DE GAUDENZI, JG; ALVAREZ, VE

Cavtat-Dubrovnik

Conferencia; Ubiquitin and SUMO: From molecular mechanisms to system-wide responses; 2017

European Molecular Biology Organization (EMBO)

Trypanosomatids are unicellular protozoans of medical and economical relevancesince they are the etiologic agents of infectious diseases in humans as well aslivestock. T. brucei lives primarily in the blood, lymph and cerebrospinal fluid in the mammalian host (bloodstream form; BSF) and in the midgut and salivary glands within the Tsetse fly (procyclic form; PCF). These contrasting environments demand rapid and complex transcriptional changes. A striking feature of African trypanosomes is their ability to maintain chronic infections as extracellular parasites. BSF trypanosomes avoid the host immune response by switching the expression of their major surface protein between Variant Surface Glycoproteins (VSG), only one of which is expressed at any given time. Intriguingly, transcriptional control in trypanosomes deviates from the eukaryotic paradigm being mostly independent of conventional promoter control, and relying instead on polycistronic transcription and trans-splicing. In this context, post-transcriptional and post-translational modifications have fundamental roles in regulation of gene expression through epigenetic mechanisms. Furthermore,trypanosomatids do possess chromatin subcompartments implicated in the control of gene expression. Critically, in BSF a highly SUMOylated focus provides an environment permissive for VSG transcription.In this work, we have characterized SUMO chain formation in vivo and in vitro. Using multiple approaches, we show that polySUMOylation (although not essential) is implicated in important biological aspects of both life cycle stages. In PCF, SUMO chains might be involved in gene regulation at the nuclear periphery. In BSF, using a mouse model of infection we demonstrate that SUMO chain dynamics could control parasitaemia and helps to establish successful long-term infections. These transgenic cell lines are useful to study non essential but very important roles for SUMO in the biology of a highly divergent organism, whose origins probably lie close to the Eukaryotic root.