Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells

Abstract 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 cy...

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Autores principales:	Gisele Fernanda Assine Picchi-Constante, Eloise Pavão Guerra-Slompo, Ana Carolina Tahira, Monica Visnieski Alcantara, Murilo Sena Amaral, Arthur Schveitzer Ferreira, Michel Batista, Cassiano Martin Batista, Samuel Goldenberg, Sergio Verjovski-Almeida, Nilson Ivo Tonin Zanchin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/096465a371e64559b0aaba9b89558b88
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spelling	oai:doaj.org-article:096465a371e64559b0aaba9b89558b882021-11-08T10:55:08ZMetacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells10.1038/s41598-021-01080-12045-2322https://doaj.org/article/096465a371e64559b0aaba9b89558b882021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01080-1https://doaj.org/toc/2045-2322Abstract 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.Gisele Fernanda Assine Picchi-ConstanteEloise Pavão Guerra-SlompoAna Carolina TahiraMonica Visnieski AlcantaraMurilo Sena AmaralArthur Schveitzer FerreiraMichel BatistaCassiano Martin BatistaSamuel GoldenbergSergio Verjovski-AlmeidaNilson Ivo Tonin ZanchinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gisele Fernanda Assine Picchi-Constante Eloise Pavão Guerra-Slompo Ana Carolina Tahira Monica Visnieski Alcantara Murilo Sena Amaral Arthur Schveitzer Ferreira Michel Batista Cassiano Martin Batista Samuel Goldenberg Sergio Verjovski-Almeida Nilson Ivo Tonin Zanchin Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
description	Abstract 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.
format	article
author	Gisele Fernanda Assine Picchi-Constante Eloise Pavão Guerra-Slompo Ana Carolina Tahira Monica Visnieski Alcantara Murilo Sena Amaral Arthur Schveitzer Ferreira Michel Batista Cassiano Martin Batista Samuel Goldenberg Sergio Verjovski-Almeida Nilson Ivo Tonin Zanchin
author_facet	Gisele Fernanda Assine Picchi-Constante Eloise Pavão Guerra-Slompo Ana Carolina Tahira Monica Visnieski Alcantara Murilo Sena Amaral Arthur Schveitzer Ferreira Michel Batista Cassiano Martin Batista Samuel Goldenberg Sergio Verjovski-Almeida Nilson Ivo Tonin Zanchin
author_sort	Gisele Fernanda Assine Picchi-Constante
title	Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
title_short	Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
title_full	Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
title_fullStr	Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
title_full_unstemmed	Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells
title_sort	metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient trypanosoma cruzi cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/096465a371e64559b0aaba9b89558b88
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Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells

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