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Going deeper into Trypanosoma cruzi chromatin regulation: identifying new players and quizzing its impact on a potential transcription control

Grant number: 18/15553-9
Support type:Research Grants - Young Investigators Grants- Phase 2
Duration: July 01, 2019 - June 30, 2024
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Julia Pinheiro Chagas da Cunha
Grantee:Julia Pinheiro Chagas da Cunha
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers: Fabíola Barbieri Holetz ; Maria Carolina Quartim Barbosa Elias Sabbaga ; Simone Guedes Calderano ; Stenio Perdigão Fragoso
Associated research grant:11/22619-7 - Nuclei and chromatin alterations through cell cycle and senescence in mammalian cells, AP.JP

Abstract

At JP1, our group described many chromatin-associated proteins as well as more than 40 histone PTMs, differentially expressed in replicate versus non-replicative life forms of Trypanosoma cruzi. Classical eu- and heterochromatin regions are presented at their nucleus and changes dramatically during differentiation from epimastigotes to metacyclics (EàM). Traditionally, these chromatin regions (and some histone PTMs) are associated to transcription regulation. However, in trypanosomes, it is general accepted that post transcriptional mechanisms govern gene expression. Thus, our main goal is to understand this apparent controversy firstly, evaluating if trypanosomes indeed have no transcription control and then, understand the potential role of chromatin regulation in this scenario possibly finding key epigenetic markers. Thus, by using parasites during E àM and in different cell cycle stages, we intend to evaluate: i. the transcription rate in a genome-wide scale; ii. if the genomic milieu interferes with the expression of a reporter gene positioned in distinct genomic loci; iii. the chromatin content of specific loci of the T.cruzi genome. These goals will be reached by using cutting-edge methodologies, such as Global Run-on sequencing (GRO-seq), locus-specific chromatin immunoprecipitation (CLASP or enCHIP) analysis, locus- specific insertion of reporter genes by CRISPR/Cas9 systems. We envisage that using this ancient organism (which has many genomic peculiarities) to understand chromatin/epigenetic regulation, will be an invaluable tool to highlight new and key epigenetic mechanisms. (AU)