Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells
PRDM (PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain-containing) transcription factors are a group of proteins that have a significant impact on organ development. In our study, we assessed the role of <i...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/19/7192 |
| _version_ | 1797552257469775872 |
|---|---|
| author | Paweł Leszczyński Magdalena Śmiech Aamir Salam Teeli Effi Haque Robert Viger Hidesato Ogawa Mariusz Pierzchała Hiroaki Taniguchi |
| author_facet | Paweł Leszczyński Magdalena Śmiech Aamir Salam Teeli Effi Haque Robert Viger Hidesato Ogawa Mariusz Pierzchała Hiroaki Taniguchi |
| author_sort | Paweł Leszczyński |
| collection | DOAJ |
| description | PRDM (PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain-containing) transcription factors are a group of proteins that have a significant impact on organ development. In our study, we assessed the role of <i>Prdm3</i> in neurogenesis and the mechanisms regulating its expression. We found that <i>Prdm3</i> mRNA expression was induced during neurogenesis and that <i>Prdm3</i> gene knockout caused premature neuronal differentiation of the P19 cells and enhanced the growth of non-neuronal cells. Interestingly, we found that <i>Gata6</i> expression was also significantly upregulated during neurogenesis. We further studied the regulatory mechanism of <i>Prdm3</i> expression. To determine the role of GATA6 in the regulation of <i>Prdm3</i> mRNA expression, we used a luciferase-based reporter assay and found that <i>Gata6</i> overexpression significantly increased the activity of the <i>Prdm3</i> promoter. Finally, the combination of retinoic acid receptors <i>α</i> and <i>β</i>, along with <i>Gata6</i> overexpression, further increased the activity of the luciferase reporter. Taken together, our results suggest that in the P19 cells, PRDM3 contributed to neurogenesis and its expression was stimulated by the synergism between GATA6 and the retinoic acid signaling pathway. |
| first_indexed | 2024-03-10T15:57:27Z |
| format | Article |
| id | doaj.art-00a63b35353b44a89b123a653235a086 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:57:27Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-00a63b35353b44a89b123a653235a0862023-11-20T15:30:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119719210.3390/ijms21197192Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 CellsPaweł Leszczyński0Magdalena Śmiech1Aamir Salam Teeli2Effi Haque3Robert Viger4Hidesato Ogawa5Mariusz Pierzchała6Hiroaki Taniguchi7Institute of Genetics and Animal Biotechnology, Laboratory for Genome Editing and Transcriptional Regulation, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandInstitute of Genetics and Animal Biotechnology, Laboratory for Genome Editing and Transcriptional Regulation, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandInstitute of Genetics and Animal Biotechnology, Laboratory for Genome Editing and Transcriptional Regulation, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandInstitute of Genetics and Animal Biotechnology, Laboratory for Genome Editing and Transcriptional Regulation, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandReproduction, Mother and Child Health, Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle (CRDSI), Quebec, QC GIV4G2, CanadaGraduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita 565-0871, JapanInstitute of Genetics and Animal Biotechnology, Department of Genomics and Biodiversity, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandInstitute of Genetics and Animal Biotechnology, Laboratory for Genome Editing and Transcriptional Regulation, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandPRDM (PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain-containing) transcription factors are a group of proteins that have a significant impact on organ development. In our study, we assessed the role of <i>Prdm3</i> in neurogenesis and the mechanisms regulating its expression. We found that <i>Prdm3</i> mRNA expression was induced during neurogenesis and that <i>Prdm3</i> gene knockout caused premature neuronal differentiation of the P19 cells and enhanced the growth of non-neuronal cells. Interestingly, we found that <i>Gata6</i> expression was also significantly upregulated during neurogenesis. We further studied the regulatory mechanism of <i>Prdm3</i> expression. To determine the role of GATA6 in the regulation of <i>Prdm3</i> mRNA expression, we used a luciferase-based reporter assay and found that <i>Gata6</i> overexpression significantly increased the activity of the <i>Prdm3</i> promoter. Finally, the combination of retinoic acid receptors <i>α</i> and <i>β</i>, along with <i>Gata6</i> overexpression, further increased the activity of the luciferase reporter. Taken together, our results suggest that in the P19 cells, PRDM3 contributed to neurogenesis and its expression was stimulated by the synergism between GATA6 and the retinoic acid signaling pathway.https://www.mdpi.com/1422-0067/21/19/7192P19 cellsPrdm3Gata6retinoic acidneurogenesisCRISPR |
| spellingShingle | Paweł Leszczyński Magdalena Śmiech Aamir Salam Teeli Effi Haque Robert Viger Hidesato Ogawa Mariusz Pierzchała Hiroaki Taniguchi Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells International Journal of Molecular Sciences P19 cells Prdm3 Gata6 retinoic acid neurogenesis CRISPR |
| title | Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells |
| title_full | Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells |
| title_fullStr | Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells |
| title_full_unstemmed | Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells |
| title_short | Deletion of the <i>Prdm3</i> Gene Causes a Neuronal Differentiation Deficiency in P19 Cells |
| title_sort | deletion of the i prdm3 i gene causes a neuronal differentiation deficiency in p19 cells |
| topic | P19 cells Prdm3 Gata6 retinoic acid neurogenesis CRISPR |
| url | https://www.mdpi.com/1422-0067/21/19/7192 |
| work_keys_str_mv | AT pawełleszczynski deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT magdalenasmiech deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT aamirsalamteeli deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT effihaque deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT robertviger deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT hidesatoogawa deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT mariuszpierzchała deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells AT hiroakitaniguchi deletionoftheiprdm3igenecausesaneuronaldifferentiationdeficiencyinp19cells |