title: Expression of non-acetylatable lysines 10 and 14 of histone H4 impairs transcription and replication in Trypanosoma cruzi.
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.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Thiago Cesar Prata
authors.initials: TC
authors.lastname: Ramos
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Vinicius Santana
authors.initials: VS
authors.lastname: Nunes
authors.affiliation: Instituto Carlos Chagas/Fiocruz-PR, Curitiba, PR, Brazil.
authors.forename: Sheila Cristina
authors.initials: SC
authors.lastname: Nardelli
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: dos Santos Pascoalino
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Nilmar Silvio
authors.initials: NS
authors.lastname: Moretti
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Antonio Augusto
authors.initials: AA
authors.lastname: Rocha
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: da Silva Augusto
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: sschenkman@unifesp.br.
authors.forename: Sergio
authors.initials: S
authors.lastname: Schenkman
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000378:metabolism; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D014349:Trypanosoma cruzi / Q000235:genetics*
chemical_list: D056488:Histone Chaperones; D006657:Histones; D015800:Protozoan Proteins; D051548:Histone Acetyltransferases; D008239:Lysine
keywords: Acetylation; Chromatin; Histone; Replication; Transcription; Trypanosoma cruzi