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Multinucleation and Polykaryon Formation is Promoted by the EhPC4 Transcription Factor in Entamoeba histolytica.
- Source :
-
Scientific reports [Sci Rep] 2016 Jan 21; Vol. 6, pp. 19611. Date of Electronic Publication: 2016 Jan 21. - Publication Year :
- 2016
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Abstract
- Entamoeba histolytica is the intestinal parasite responsible for human amoebiasis that is a leading cause of death in developing countries. In this protozoan, heterogeneity in DNA content, polyploidy and genome plasticity have been associated to alterations in mechanisms controlling DNA replication and cell division. Studying the function of the transcription factor EhPC4, we unexpectedly found that it is functionally related to DNA replication, and multinucleation. Site-directed mutagenesis on the FRFPKG motif revealed that the K127 residue is required for efficient EhPC4 DNA-binding activity. Remarkably, overexpression of EhPC4 significantly increased cell proliferation, DNA replication and DNA content of trophozoites. A dramatically increase in cell size resulting in the formation of giant multinucleated trophozoites (polykaryon) was also found. Multinucleation event was associated to cytokinesis failure leading to abortion of ongoing cell division. Consistently, genome-wide profiling of EhPC4 overexpressing trophozoites revealed the up-regulation of genes involved in carbohydrates and nucleic acids metabolism, chromosome segregation and cytokinesis. Forced overexpression of one of these genes, EhNUDC (nuclear movement protein), led to alterations in cytokinesis and partially recapitulated the multinucleation phenotype. These data indicate for the first time that EhPC4 is associated with events related to polyploidy and genome stability in E. histolytica.
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Cell Proliferation
Chromosome Segregation
Conserved Sequence
Cytokinesis
DNA genetics
DNA metabolism
DNA Replication
Evolution, Molecular
Gene Expression
Models, Molecular
Protein Conformation
Protein Interaction Domains and Motifs
Transcription Factors chemistry
Entamoeba histolytica genetics
Entamoeba histolytica metabolism
Polyploidy
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26792358
- Full Text :
- https://doi.org/10.1038/srep19611