Zfp281 inhibits the pluripotent-to-totipotent state trasition in mouse embryonic stem cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE201478 | GEO | 2022/04/26
REPOSITORIES: GEO
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Project description:The cell-fate transition between pluripotent and totipotent states determines embryonic development and the first cell-lineage segregation. However, limited by the scarcity of totipotent embryos, regulators on this transition remain largely elusive. A novel model to study the transition has been recently established, named the 2-cell-like (2C-like) model. The 2C-like cells are rare totipotent-like cells in the mouse embryonic stem cell (mESC) culture. Pluripotent mESCs can spontaneously transit into and out of the 2C-like state. We previously dissected the transcriptional roadmap of the transition. In this study, we revealed that Zfp281 is a novel regulator for the pluripotent-to-totipotent transition in mESCs. Zfp281 is a transcriptional factor involved in the cell-fate transition. Our study shows that Zfp281 represses transcripts upregulated during the 2C-like transition via Tet1 and consequentially inhibits mESCs from transiting into the 2C-like state. Interestingly, we found that the inhibitory effect of Zfp281 on the 2C-like transition leads to an impaired 2C-like-transition ability in primed-state mESCs. Altogether, our study reveals a novel mediator for the pluripotent-to-totipotent state transition in mESCs and provides insights into the dynamic transcriptional control of the transition.
| S-EPMC9163740 | biostudies-literature
Project description:Zfp281 inhibits the pluripotent-to-totipotent state trasition in mouse embryonic stem cells
| PRJNA831856 | ENA
Project description:The progression and transition between the naïve, formative, and primed pluripotent states are accompanied by a sharp activation of the de novo DNA methyltransferases and the reorganization of transcriptional and epigenetic landscapes. Here we identified Zinc Finger Protein 281 (ZFP281) as an essential factor in the formative-to-primed pluripotent state transition. Using a knockout mouse model and a knockin degron cell system, we revealed that transcription of Dnmt3a/3b depends on the activity of ZFP281 in embryonic stem cells, epiblast-like cells, and epiblast stem cells. Mechanically, chromatin-bound ZFP281 and DNA hydroxylase TET1 are decreased in the formative state but recovered in the primed state to compete with DNMT3A/3B for establishing the DNA methylation and gene expression programs of primed pluripotency. In addition, chromatin occupancy of ZFP281 and TET1 depend on the R-loop structures formed at the ZFP281 target gene promoters devoid of DNA methylation. Our study demonstrates a comprehensive role of ZFP281 in modulating DNA methylation and demethylation for the establishment and maintenance of primed pluripotency.
2023-12-14 | GSE227093 | GEO
Project description:The progression and transition between the naïve, formative, and primed pluripotent states are accompanied by a sharp activation of the de novo DNA methyltransferases and the reorganization of transcriptional and epigenetic landscapes. Here we identified Zinc Finger Protein 281 (ZFP281) as an essential factor in the formative-to-primed pluripotent state transition. Using a knockout mouse model and a knockin degron cell system, we revealed that transcription of Dnmt3a/3b depends on the activity of ZFP281 in embryonic stem cells, epiblast-like cells, and epiblast stem cells. Mechanically, chromatin-bound ZFP281 and DNA hydroxylase TET1 are decreased in the formative state but recovered in the primed state to compete with DNMT3A/3B for establishing the DNA methylation and gene expression programs of primed pluripotency. In addition, chromatin occupancy of ZFP281 and TET1 depend on the R-loop structures formed at the ZFP281 target gene promoters devoid of DNA methylation. Our study demonstrates a comprehensive role of ZFP281 in modulating DNA methylation and demethylation for the establishment and maintenance of primed pluripotency.
2023-12-14 | GSE226041 | GEO
Project description:The progression and transition between the naïve, formative, and primed pluripotent states are accompanied by a sharp activation of the de novo DNA methyltransferases and the reorganization of transcriptional and epigenetic landscapes. Here we identified Zinc Finger Protein 281 (ZFP281) as an essential factor in the formative-to-primed pluripotent state transition. Using a knockout mouse model and a knockin degron cell system, we revealed that transcription of Dnmt3a/3b depends on the activity of ZFP281 in embryonic stem cells, epiblast-like cells, and epiblast stem cells. Mechanically, chromatin-bound ZFP281 and DNA hydroxylase TET1 are decreased in the formative state but recovered in the primed state to compete with DNMT3A/3B for establishing the DNA methylation and gene expression programs of primed pluripotency. In addition, chromatin occupancy of ZFP281 and TET1 depend on the R-loop structures formed at the ZFP281 target gene promoters devoid of DNA methylation. Our study demonstrates a comprehensive role of ZFP281 in modulating DNA methylation and demethylation for the establishment and maintenance of primed pluripotency.
2023-12-14 | GSE226040 | GEO
Project description:The progression and transition between the naïve, formative, and primed pluripotent states are accompanied by a sharp activation of the de novo DNA methyltransferases and the reorganization of transcriptional and epigenetic landscapes. Here we identified Zinc Finger Protein 281 (ZFP281) as an essential factor in the formative-to-primed pluripotent state transition. Using a knockout mouse model and a knockin degron cell system, we revealed that transcription of Dnmt3a/3b depends on the activity of ZFP281 in embryonic stem cells, epiblast-like cells, and epiblast stem cells. Mechanically, chromatin-bound ZFP281 and DNA hydroxylase TET1 are decreased in the formative state but recovered in the primed state to compete with DNMT3A/3B for establishing the DNA methylation and gene expression programs of primed pluripotency. In addition, chromatin occupancy of ZFP281 and TET1 depend on the R-loop structures formed at the ZFP281 target gene promoters devoid of DNA methylation. Our study demonstrates a comprehensive role of ZFP281 in modulating DNA methylation and demethylation for the establishment and maintenance of primed pluripotency.
2023-12-14 | GSE247461 | GEO
Project description:Zfp281 is a partner protein of Nanog. To identify potential target genes of Zfp281, we generated Zfp281 null ESCs using gene targeting, and compared transcriptomic changes between multiple lines of wildtype, heterozygous and null ESCs. Total 8 ESC lines: 3 wildtype lines, 2 heterozygous lines, and 3 null lines.
2011-12-01 | E-GEOD-30293 | biostudies-arrayexpress
Project description:Totipotency refers to the ability of a cell to generate all of the cell types of an organism. Unlike pluripotency, the establishment of totipotency is poorly understood. In mouse embryonic stem cells, Dux drives a small percentage of cells into a totipotent state by expressing 2-cell-embryo-specific transcripts. To understand how this transition takes place, we performed single-cell RNA-seq, which revealed a two-step transcriptional reprogramming process characterized by downregulation of pluripotent genes in the first step and upregulation of the 2-cell-embryo-specific elements in the second step. To identify factors controlling the transition, we performed a CRISPR-Cas9-mediated screen, which revealed Myc and Dnmt1 as two factors preventing the transition. Mechanistic studies demonstrate that Myc prevents downregulation of pluripotent genes in the first step, while Dnmt1 impedes 2-cell-embryo-specific gene activation in the second step. Collectively, the findings of our study reveal insights into the establishment and regulation of the totipotent state in mouse embryonic stem cells.
| S-EPMC7137718 | biostudies-literature
Project description:Pluripotent cell identity comprises a spectrum of cell states including naive and primed states, which are typified by mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs), respectively. Here we define a pluripotent cell fate (PCF) gene signature based on RNA-seq analysis associated with naive and primed pluripotency acquisition, and identify Zfp281 as a key transcriptional regulator for primed pluripotency and also as a barrier to achieve the naive pluripotency of both mouse and human ESCs. RNA sequencing analysis was performed in WT and Zfp281 null mouse embryonic stem cells under different pluripotent culture conditions. RNA-seq Experiments were carry out in two biological replciates. Genome binding/occupancy profiling of Zfp281 was performed in mouse embryonic stem cells by ChIP sequencing.
2016-06-28 | E-GEOD-81044 | biostudies-arrayexpress
Project description:Pluripotent cell identity comprises a spectrum of cell states including naive and primed states, which are typified by mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs), respectively. Here we define a pluripotent cell fate (PCF) gene signature based on RNA-seq analysis associated with naive and primed pluripotency acquisition, and identify Zfp281 as a key transcriptional regulator for primed pluripotency and also as a barrier to achieve the naive pluripotency of both mouse and human ESCs. RNA sequencing analysis was performed in WT and Zfp281 null mouse embryonic stem cells under different pluripotent culture conditions. RNA-seq Experiments were carry out in two biological replciates. Genome binding/occupancy profiling of Zfp281 was performed in mouse embryonic stem cells by ChIP sequencing.
2016-06-28 | E-GEOD-81042 | biostudies-arrayexpress