期刊
SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-01080-1
关键词
-
资金
- Seventh Framework Programme of the European Commission [EC-GA 602080]
- Fundacao Butantan
- Brazilian National Research Council (CNPq)
- Research Foundation from the state of Parana (FapPR) [41/2018]
- INOVA research program from FIOCRUZ
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [312195/2015-0, 304167/2019-3, 306709/2016-3, 306646/2019-6]
This study investigated the function of T. cruzi histone deacetylase 4 (TcHDAC4) and found that TcHDAC4 deficiency leads to chromatin alterations and abnormal gene expression regulation.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据