Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
| Autor: | Cassiano Martin Batista, Gisele Fernanda Assine Picchi-Constante, Ana Carolina Tahira, Nilson Ivo Tonin Zanchin, Murilo S. Amaral, Michel Batista, Arthur Schveitzer Ferreira, Samuel Goldenberg, Sergio Verjovski-Almeida, Eloise P. Guerra-Slompo, Monica Visnieski Alcantara |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Science Trypanosoma cruzi Mutant Cell Culture Techniques Protozoan Proteins Gene Expression Histone Deacetylases Article Gene expression parasitic diseases Chlorocebus aethiops Animals Humans Chagas Disease Transcriptomics Gene Vero Cells Regulation of gene expression Life Cycle Stages Multidisciplinary biology Acetylation biology.organism_classification HDAC4 Chromatin Cell biology Repressor Proteins Histone Gene Expression Regulation biology.protein Trypanosoma Medicine Epigenetics Protein Processing Post-Translational Post-translational modifications |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-18 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Trypanosoma cruzi—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 T. cruzi histone deacetylase 4 (TcHDAC4). We show that, although TcHDAC4 is not essential for viability, metacyclic trypomastigote TcHDAC4 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 TcHDAC4. Gene expression analyses identified three chromosomes with overrepresented regions of differentially expressed genes in the TcHDAC4 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 TcHDAC4 participates in gene expression regulation during T. cruzi differentiation. |
| Databáze: | OpenAIRE |
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