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

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)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LUND, PEDER J.; LOPES, MARIANA; SIDOLI, SIMONE; CORADIN, MARIEL; DE LUNA VITORINO, FRANCISCA NATHALIA; CHAGAS DA CUNHA, JULIA PINHEIRO; GARCIA, BENJAMIN A. FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence. MOLECULAR OMICS, v. 17, n. 5, p. 725-739, OCT 11 2021. Web of Science Citations: 0.
LUND, PEDER J.; LOPES, MARIANA; SIDOLI, SIMONE; CORADIN, MARIEL; DE LUNA VITORINO, FRANCISCA NATHALIA; CHAGAS DA CUNHA, JULIA PINHEIRO; GARCIA, BENJAMIN A. FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence. MOLECULAR OMICS, JUN 2021. Web of Science Citations: 0.
LIMA, ALEX R. J.; DE ARAUJO, CHRISTIANE B.; BISPO, SALOE; PATANE, JOSE; SILBER, ARIEL M.; ELIAS, M. CAROLINA; DA CUNHA, JULIA P. C. Nucleosome landscape reflects phenotypic differences in Trypanosoma cruzi life forms. PLOS PATHOGENS, v. 17, n. 1 JAN 2021. Web of Science Citations: 0.
AZEVEDO, HATYLAS; PESSOA, GUILHERME CAVALCANTE; DE LUNA VITORINO, FRANCISCA NATHALIA; NSENGIMANA, JEREMIE; NEWTON-BISHOP, JULIA; REIS, EDUARDO MORAES; DA CUNHA, JULIA PINHEIRO CHAGAS; JASIULIONIS, MIRIAM GALVONAS. Gene co-expression and histone modification signatures are associated with melanoma progression, epithelial-to-mesenchymal transition, and metastasis. CLINICAL EPIGENETICS, v. 12, n. 1 AUG 24 2020. Web of Science Citations: 0.
DE LIMA, LOYZE P.; POUBEL, SALOE BISPO; YUAN, ZUO-FEI; ROSON, JULIANA NUNES; DE LUNA VITORINO, FRANCISCA NATHALIA; HOLETZ, FABIOLA BARBIERI; GARCIA, BENJAMIN A.; CHAGAS DA CUNHA, JULIA PINHEIRO. Improvements on the quantitative analysis of Trypanosoma cruzi histone post translational modifications: Study of changes in epigenetic marks through the parasite's metacyclogenesis and life cycle. JOURNAL OF PROTEOMICS, v. 225, APR 15 2020. Web of Science Citations: 0.

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