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

Thiago Cesar Prata Ramos, Vinicius Santana Nunes, Sheila Cristina Nardelli, Bruno Dos Santos Pascoalino, Nilmar Silvio Moretti, Antonio Augusto Rocha, Leonardo Da Silva Augusto, Sergio Schenkman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalMolecular and Biochemical Parasitology
Volume204
Issue number1
DOIs
StatePublished - Nov 2015
Externally publishedYes

Keywords

  • Acetylation
  • Chromatin
  • Histone
  • Replication
  • Transcription
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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