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 Opportunities: Research Grants - Young Investigators Grants - Phase 2
• Start date: July 01, 2019
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Julia Pinheiro Chagas da Cunha
• Grantee: Julia Pinheiro Chagas da Cunha
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated 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
• Associated research grant(s): 24/02275-1 - Unveiling new perspectives on Trypanosoma cruzi chromatin through locus-specific immunoprecipitation, AP.R
• Associated scholarship(s): 22/15610-8 - Identification of transcription start sites and possible promoter regions in Trypanosoma cruzi, BP.DR; 23/08391-0 - Describing new players at Trypanosoma cruzi chromatin by locus-specific chromatin immunoprecipitation, BP.PD; 22/12897-4 - Evidencing centromeric regions in Trypanosoma cruzi: an in silico and experimental approach, BP.MS; + associated scholarships 19/16033-1 - Study in the transcription start and terminal sites of RNA polymerase II from Trypanosoma cruzi, BP.DR; 21/11419-9 - Trypanosoma cruzi chromatin milieu: an active or dormant character on reporter genes transcription?, BP.DD; 21/03219-0 - Interrogation of a potential transcription regulation in Trypanosoma cruzi by evaluation of nascent transcripts genome-widely, BP.PD; 20/02708-4 - Exploring the role of chromatin-associated proteins detected in Trypanosoma cruzi, BP.MS; 19/19834-5 - Describing new players at Trypanosoma cruzi chromatin by locus-specific chromatin immunoprecipitation, BP.PD - associated scholarships

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)

Scientific publications

(13)

(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)

FLORENTINO, P. T. V.; VITORINO, F. N. L.; MENDES, D.; DA CUNHA, J. P. C.; MENCK, C. F. M.. Trypanosoma cruzi infection changes the chromatin proteome profile of infected human cells. JOURNAL OF PROTEOMICS, v. 272, p. 11-pg., 2023-02-10. (13/07467-1, 19/19435-3, 17/18344-9, 13/08028-1, 18/15553-9)

NASCIMENTO, JANAINA DE FREITAS; DAMASCENO, FLAVIA SILVA; MARSICCOBETRE, SABRINA; VITORINO, FRANCISCA NATALIA DE LUNA; ACHJIAN, RENAN WEEGE; DA CUNHA, JULIA PINHEIRO CHAGAS; SILBER, ARIEL MARIANO. Branched-chain amino acids modulate the proteomic profile of Trypanosoma cruzi metacyclogenesis induced by proline. PLoS Neglected Tropical Diseases, v. 18, n. 10, p. 25-pg., 2024-10-01. (18/15553-9, 21/12938-0)

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, p. 24-pg., 2020-08-24. (17/18344-9, 18/15553-9, 18/20775-0, 14/13663-0, 18/04254-0)

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. (18/15553-9, 19/19690-3, 18/14432-3, 16/50050-2, 13/07467-1)

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. (16/24881-4, 15/04867-4, 13/07467-1, 17/15835-1, 18/15553-9, 11/22619-7, 17/18344-9)

VITORINO, FRANCISCA N. DE LUNA; LEVY, MICHAELLA J.; WAILEMANN, ROSANGELA A. MANSANO; LOPES, MARIANA; SILVA, MARIANA LOTERIO; SARDIU, MIHAELA E.; GARCIA, BENJAMIN A.; MOTTA, MARIA CRISTINA MACHADO; OLIVEIRA, CARLA COLUMBANO; ARMELIN, HUGO AGUIRRE; et al. The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus. Journal of Cell Science, v. 136, n. 22, p. 13-pg., 2023-11-01. (17/18344-9, 11/22619-7, 13/07467-1, 17/06104-3, 18/15553-9, 19/17675-7)

JERONIMO LIMA, ALEX RANIERI; DE SOUSA SILVA, HERBERT GUIMARAES; POUBEL, SALOE; ROSON, JULIANA NUNES; OLIVEIRA DE LIMA, LOYZE PAOLA; COSTA-SILVA, HELLIDA MARINA; GONCALVES, CAMILA SILVA; GALANTE, PEDRO A. F.; HOLETZ, FABIOLA; MOTTA, MARIA CRISTINA MACHADO M.; et al. Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci. EPIGENETICS & CHROMATIN, v. 15, n. 1, p. 16-pg., 2022-06-01. (13/07467-1, 18/15553-9, 20/02708-4, 18/14432-3, 19/19834-5, 19/19690-3)

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. (11/22619-7, 16/24881-4, 17/15835-1, 18/15553-9, 15/04867-4, 17/18344-9, 13/07467-1)

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. (17/18344-9, 18/20775-0, 14/13663-0, 18/04254-0, 18/15553-9)

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. (18/21785-0, 17/06104-3, 18/14432-3, 18/15553-9, 13/07467-1, 17/18344-9)

FRAGOSO, MARIANA SAYURI ISHIKAWA; DE SIQUEIRA, CAROLINE MORAES; VITORINO, FRANCISCA NATHALIA LUNA; VIEIRA, ALEXANDRE ZANATTA; MARTINS-DUARTE, ERICA SANTOS; FAORO, HELISSON; DA CUNHA, JULIA PINHEIRO CHAGAS; AVILA, ANDREA RODRIGUES; NARDELLI, SHEILA CRISTINA. TgKDAC4: A Unique Deacetylase of Toxoplasma's Apicoplast. MICROORGANISMS, v. 11, n. 6, p. 16-pg., 2023-06-01. (18/15553-9)

ROSON, JULIANA NUNES; VITARELLI, MARCELA DE OLIVEIRA J.; COSTA-SILVA, HELLIDA MARINA; PEREIRA, KAMILLE SCHMITT; PIRES, DAVID DA SILVA; LOPES, LETICIA DE SOUSA; CORDEIRO, BARBARA; KRAUS, AMELIE; CRUZ, KARIN NAVARRO TOZZI; CALDERANO, SIMONE GUEDES; et al. 2B.V demarcates divergent strand-switch regions, some tDNA loci, and genome compartments in Trypanosoma cruzi and affects parasite differentiation and host cell invasio. PLOS PATHOGENS, v. 18, n. 2, FEB 2022. (18/15553-9, 16/50050-2, 17/06104-3, 19/04483-2, 19/16033-1, 13/07467-1, 19/19834-5)

MENEZES, ANA PAULA; MURILLO, ANA MILENA; DE CASTRO, CAMILA GACHET; BELLINI, NATALIA KARLA; TOSI, LUIZ RICARDO ORSINI; THIEMANN, OTAVIO HENRIQUE; ELIAS, MARIA CAROLINA; SILBER, ARIEL MARIANO; DA CUNHA, JULIA PINHEIRO CHAGAS. Navigating the boundaries between metabolism and epigenetics in trypanosomes. Trends in Parasitology, v. 39, n. 8, p. 14-pg., 2023-08-01. (21/12469-0, 18/14432-3, 18/15553-9, 21/03219-0, 19/21354-1, 20/00694-6)