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Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE81045 | GEO | 2016/06/28

SECONDARY ACCESSION(S): PRJNA320355

REPOSITORIES: GEO

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Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-28 | E-GEOD-81045 | biostudies-arrayexpress

Zfp281 Coordinates Opposing Functions of Tet1 and Tet2 in Pluripotent States.

Project description:Pluripotency is increasingly recognized as a spectrum of cell states defined by their growth conditions. Although naive and primed pluripotency states have been characterized molecularly, our understanding of events regulating state acquisition is wanting. Here, we performed comparative RNA sequencing of mouse embryonic stem cells (ESCs) and defined a pluripotent cell fate (PCF) gene signature associated with acquisition of naive and primed pluripotency. We identify Zfp281 as a key transcriptional regulator for primed pluripotency that also functions as a barrier toward achieving naive pluripotency in both mouse and human ESCs. Mechanistically, Zfp281 interacts with Tet1, but not Tet2, and its direct transcriptional target, miR-302/367, to negatively regulate Tet2 expression to establish and maintain primed pluripotency. Conversely, ectopic Tet2 alone, but not Tet1, efficiently reprograms primed cells toward naive pluripotency. Our study reveals a molecular circuitry in which opposing functions of Tet1 and Tet2 control acquisition of alternative pluripotent states.

| S-EPMC5010473 | biostudies-literature

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States [RNA-Seq]

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

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States [ChIP-Seq]

2016-06-28 | E-GEOD-81042 | biostudies-arrayexpress

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States [ChIP-Seq]

2016-06-28 | GSE81042 | GEO

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States [RNA-Seq]

2016-06-28 | GSE81044 | GEO

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States

Project description:Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States

| PRJNA320355 | ENA

ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions.

Project description:The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates the development of the epiblast in vivo during the peri-implantation period of mammalian development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events occurring during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knock-in cell models, we uncover the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells. Chromatin co-occupancy of ZFP281 and DNA hydroxylase TET1, dependent on the formation of R loops in ZFP281-targeted gene promoters, undergoes a "high-low-high" bimodal pattern regulating dynamic DNA methylation and gene expression during the naïive-formative-primed transitions. ZFP281 also safeguards DNA methylation in maintaining primed pluripotency. Our study demonstrates a previously unappreciated role for ZFP281 in coordinating DNMT3A/3B and TET1 functions to promote pluripotent state transitions.

| S-EPMC10055359 | biostudies-literature

ZFP281 coordinates DNMT3 and TET1 in pluripotent state transitions

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-14 | GSE226042 | GEO

ZFP281 coordinates DNMT3 and TET1 in pluripotent state transitions [STEM-seq]

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

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