Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi

Author(s):Show less -

Leandro de Jesus, Teresa Cristina ^{[1, 2]} ; Nunes, Vinicius Santana ^[3] ; Lopes, Mariana de Camargo ^[1] ; Martil, Daiana Evelin ^[2] ; Iwai, Leo Kei ^[1] ; Moretti, Nilmar Silvio ^[3] ; Machado, Fabricio Castro ^[3] ; de Lima-Stein, Mariana L. ^[3] ; Thiemann, Otavio Henrique ^[2] ; Elias, Maria Carolina ^[1] ; Janzen, Christian ^[4] ; Schenkman, Sergio ^[3] ; Chagas da Cunha, Julia Pinheiro ^[1]

Affiliation

^[1] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Especial Ciclo Celular, BR-05503900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Dept Fis & Informat, BR-13563120 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04039032 Sao Paulo - Brazil

^[4] Univ Wurzburg, Bioctr, Theodor Boveri Inst, Dept Cell & Dev Biol, D-97070 Wurzburg - Germany

• Document type: Journal article
• Source: JOURNAL OF PROTEOME RESEARCH; v. 15, n. 6, p. 2039-2051, JUN 2016.
• Web of Science Citations: 12

Abstract

Histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, DNA damage repair, and chromosome condensation. In early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based processes. Here, by using high-resolution mass spectrometry, we identified and quantified histone post-translational modifications in two life cycle stages of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. We detected 44 new modifications, namely: 18 acetylations, seven monomethylations, seven dimethylations, seven trimethylations, and four phosphorylations. We found that replicative (epimastigote stage) contains more histone modifications than nonreplicative and infective parasites (trypomastigote stage). Acetylations of lysines at the C-terminus of histone H2A and methylations of lysine 23 of histone H3 were found to be enriched in trypomastigotes. In contrast, phosphorylation in serine 23 of H2B and methylations of lysine 76 of histone H3 predominates in proliferative states. The presence of one or two methylations in the lysine 76 was found in cells undergoing mitosis and cytokinesis, typical of proliferating parasites. Our findings provide new insights into the role of histone modifications related to the control of gene expression and cell-cycle regulation in an early divergent organism. (AU)

• FAPESP's process: 14/01577-2 - The role of eIF2 phosphorylation and sirtuins in the multiplication and differentiation of intracellular Trypanosoma cruzi
• Grantee: Fabrício Castro Machado
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/51973-3 - Cell signaling mechanism of Trypanosoma in response to nutritional alterations and genotoxic agents
• Grantee: Sergio Schenkman
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 08/57910-0 - National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases
• Grantee: Richard Charles Garratt
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 11/06087-5 - Identification and characterization of replication origins in Trypanosoma and Leishmania
• Grantee: Teresa Cristina Leandro de Jesus
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/04867-4 - Nuclear proteome alterations induced by growth factor along cell cycle in mice tumour cells
• Grantee: Mariana de Camargo Lopes
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 14/03714-7 - Interaction of Sir2 protein with translation initiation factors in Trypanosoma
• Grantee: Vinícius Santana Nunes
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 11/22619-7 - Nuclei and chromatin alterations through cell cycle and senescence in mammalian cells
• Grantee: Julia Pinheiro Chagas da Cunha
• Support type: Research Grants - Young Investigators Grants