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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Expression of non-acetylatable lysines 10 and 14 of histone H4 impairs transcription and replication in Trypanosoma cruzi

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Author(s):
Prata Ramos, Thiago Cesar [1] ; Nunes, Vinicius Santana [1] ; Nardelli, Sheila Cristina [2] ; Pascoalino, Bruno dos Santos [1] ; Moretti, Nilmar Silvio [1] ; Rocha, Antonio Augusto [1] ; Augusto, Leonardo da Silva [1] ; Schenkman, Sergio [1]
Total Authors: 8
Affiliation:
[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, SP - Brazil
[2] Inst Carlos Chagas Fiocruz PR, Curitiba, PR - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Molecular and Biochemical Parasitology; v. 204, n. 1, p. 1-10, NOV 2015.
Web of Science Citations: 8
Abstract

The histone H4 from Trypanosomatids diverged from other eukaryotes in the N-terminus, a region that undergoes post-translation modifications involved in the control of gene expression, DNA replication, and chromatin assembly. Nonetheless, the N-terminus of Trypanosoma cruzi histone H4 is mainly acetylated at lysine 4. The lysines 10 and 14 are also acetylated, although at less extent, increasing during the S phase or after DNA damage, which suggests a regulatory function. Here, we investigated the roles of these acetylations by expressing non-acetylated forms of histone H4 in T. cruzi. We found that histone H4 containing arginines at positions 10 or 14, to prevent acetylation were transported to the nucleus and inserted into the chromatin. However, their presence, even at low levels, interfered with DNA replication and transcription, causing a significant growth arrest of the cells. The absence of acetylation also increased the amount of soluble endogenous histones H3 and H4 and affected the interaction with Asf1, a histone chaperone. Therefore, acetylation of lysines 10 and 14 of the histone H4 in trypanosomes could be required for chromatin assembly and/or remodeling required for transcription and replication. (C) 2015 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 11/51973-3 - Cell signaling mechanism of Trypanosoma in response to nutritional alterations and genotoxic agents
Grantee:Sergio Schenkman
Support Opportunities: Research Projects - Thematic Grants