Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells
Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation....
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MDPI AG
2022-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/10/1745 |
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| author | Valeria Lucci Elena De Marino Daniela Tagliaferri Stefano Amente Alessandra Pollice Viola Calabrò Maria Vivo Geppino Falco Tiziana Angrisano |
| author_facet | Valeria Lucci Elena De Marino Daniela Tagliaferri Stefano Amente Alessandra Pollice Viola Calabrò Maria Vivo Geppino Falco Tiziana Angrisano |
| author_sort | Valeria Lucci |
| collection | DOAJ |
| description | Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame’s downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, <i>Cdk8</i> and <i>Cdkn2d</i>, bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the <i>Cdk8</i> and <i>Cdkn2d</i> genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of naïve pluripotency. |
| first_indexed | 2024-03-09T12:17:16Z |
| format | Article |
| id | doaj.art-e3fbd4ad3cfc45cb81724512d3a6c695 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T12:17:16Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e3fbd4ad3cfc45cb81724512d3a6c6952023-11-30T22:45:07ZengMDPI AGGenes2073-44252022-09-011310174510.3390/genes13101745Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem CellsValeria Lucci0Elena De Marino1Daniela Tagliaferri2Stefano Amente3Alessandra Pollice4Viola Calabrò5Maria Vivo6Geppino Falco7Tiziana Angrisano8Department of Biology, University of Naples “Federico II”, 80147 Naples, ItalyDepartment of Biology, University of Naples “Federico II”, 80147 Naples, ItalyBiogem Scarl, Istituto di Ricerche Genetiche “Gaetano Salvatore”, 83031 Ariano Irpino, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Biology, University of Naples “Federico II”, 80147 Naples, ItalyDepartment of Biology, University of Naples “Federico II”, 80147 Naples, ItalyDepartment of Chemistry and Biology, University of Salerno, 84084 Fisciano, ItalyDepartment of Biology, University of Naples “Federico II”, 80147 Naples, ItalyDepartment of Biology, University of Naples “Federico II”, 80147 Naples, ItalyEmbryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame’s downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, <i>Cdk8</i> and <i>Cdkn2d</i>, bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the <i>Cdk8</i> and <i>Cdkn2d</i> genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of naïve pluripotency.https://www.mdpi.com/2073-4425/13/10/1745PRAMEembryo stem cellRA-resistant |
| spellingShingle | Valeria Lucci Elena De Marino Daniela Tagliaferri Stefano Amente Alessandra Pollice Viola Calabrò Maria Vivo Geppino Falco Tiziana Angrisano Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells Genes PRAME embryo stem cell RA-resistant |
| title | Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells |
| title_full | Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells |
| title_fullStr | Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells |
| title_full_unstemmed | Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells |
| title_short | Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells |
| title_sort | identification of i cdk8 i and i cdkn2d i as new prame target genes in 2c like embryonic stem cells |
| topic | PRAME embryo stem cell RA-resistant |
| url | https://www.mdpi.com/2073-4425/13/10/1745 |
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