Multinucleation and Polykaryon Formation is Promoted by the EhPC4 Transcription Factor in Entamoeba histolytica
| Autor: | Olga Hernández de la Cruz, Christian Weber, César López-Camarillo, Esther Orozco, José Díaz-Chávez, Nancy Guillén, Laurence A. Marchat, Arturo Rojo-Domínguez, Itzel Lopez Rosas, Luis Javier Herrera |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA Replication Models Molecular Cell division Protein Conformation Amino Acid Motifs Gene Expression Biology Article Evolution Molecular Polyploidy 03 medical and health sciences Entamoeba histolytica chemistry.chemical_compound Chromosome Segregation Protein Interaction Domains and Motifs Amino Acid Sequence Transcription factor Gene Conserved Sequence Cell Proliferation Cytokinesis Multidisciplinary Binding Sites 030102 biochemistry & molecular biology Cell growth DNA replication DNA biology.organism_classification Molecular biology Cell biology 030104 developmental biology chemistry Transcription Factors |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep19611 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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