• Media type: E-Article
  • Title: Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
  • Contributor: Picchi-Constante, Gisele Fernanda Assine; Guerra-Slompo, Eloise Pavão; Tahira, Ana Carolina; Alcantara, Monica Visnieski; Amaral, Murilo Sena; Ferreira, Arthur Schveitzer; Batista, Michel; Batista, Cassiano Martin; Goldenberg, Samuel; Verjovski-Almeida, Sergio; Zanchin, Nilson Ivo Tonin
  • Published: Springer Science and Business Media LLC, 2021
  • Published in: Scientific Reports, 11 (2021) 1
  • Language: English
  • DOI: 10.1038/s41598-021-01080-1
  • ISSN: 2045-2322
  • Keywords: Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p><jats:italic>Trypanosoma cruzi</jats:italic>—the causative agent of Chagas disease—like other kinetoplastids, relies mostly on post-transcriptional mechanisms for regulation of gene expression. However, trypanosomatids undergo drastic changes in nuclear architecture and chromatin structure along their complex life cycle which, combined with a remarkable set of reversible histone post-translational modifications, indicate that chromatin is also a target for control of gene expression and differentiation signals in these organisms. Chromatin-modifying enzymes have a direct impact on gene expression programs and DNA metabolism. In this work, we have investigated the function of <jats:italic>T. cruzi</jats:italic> histone deacetylase 4 (<jats:italic>Tc</jats:italic>HDAC4). We show that, although <jats:italic>Tc</jats:italic>HDAC4 is not essential for viability, metacyclic trypomastigote <jats:italic>Tc</jats:italic>HDAC4 null mutants show a thin cell body and a round and less condensed nucleus located very close to the kinetoplast. Sixty-four acetylation sites were quantitatively evaluated, which revealed H2AT85ac, H4K10ac and H4K78ac as potential target sites of <jats:italic>Tc</jats:italic>HDAC4. Gene expression analyses identified three chromosomes with overrepresented regions of differentially expressed genes in the <jats:italic>Tc</jats:italic>HDAC4 knockout mutant compared with the wild type, showing clusters of either up or downregulated genes. The adjacent chromosomal location of some of these genes indicates that <jats:italic>Tc</jats:italic>HDAC4 participates in gene expression regulation during <jats:italic>T. cruzi</jats:italic> differentiation.</jats:p>
  • Access State: Open Access