TRYPANOSOMA CRUZI HIGH MOBILITY GROUP B PROTEIN (TCHMGB) CAN ALTER CHROMATIN STRUCTURE AND AFFECTS IMPORTANT PARASITE FUNCTIONS

TAVERNELLI LUIS; MOTTA, MARIA CRISTINA; ALONSO, VICTORIA LUCÍA; GONÇALVES CAMILA; CRIBB, PAMELA; SERRA, ESTEBAN

Caxambú

Encuentro; XXXIII Annual Meeting of the Brazilian Society of Protozoology; 2017

HIGH MOBILITY GROUP Bs are abundant non-histone chromatin proteins. The DNA-HMGBinteraction produces changes in chromatin structure thus affecting important nuclear processeslike transcription, replication, recombination, DNA repair and chromosome segregation.TcHMGB, the HMGB from Trypanosoma cruzi, has two "HMG box" DNA binding domains and aunique N-terminal sequence that bears a nuclear localization signal (NLS) and a "DEK-Cterminal? domain. We previously demonstrated that TcHMGB is expressed in the nucleus in allthe parasite life stages and has architectural properties on DNA structure like its mammalianorthologs. Given the TcHMGB "architectural" properties, the particular characteristics oftranscription in trypanosomatids and evidence gathered about epigenetic mechanismscontrolling gene expression, we decided to evaluate the role of TcHMGB in vivo.With the aim of investigating TcHMGB functions, we constructed transgenic parasites capableof overexpressing the protein under tetracycline induction. We showed that TcHMGB caninteract with chromatin DNA in vivo, altering where an overexpression of the protein altered thechromatin state in epimastigotes making it more sensible to micrococcal nuclease treatment.Overexpression of TcHMGB caused a dramatic decrease in epimastigotes growth and an arrestin G2/M phase. Also, other stages´ functions resulted impaired: we observed a decrease intrypomastigote in vitro infectivity on Vero cells, amastigotes proliferation and trypomastigotesrelease from infected cells in vitro in overexpressing parasites. These results suggest thattrypanosomatid HMGB proteins can be considered pleiotropic players involved in trypanosomeskey cellular processes, and they should also be considered as putative actors in Chagasdisease pathogenesis.