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

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

PROVIDER: PRJNA320355 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3471540.fastq.gz	Fastqsanger.gz
	SRR3471550.fastq.gz	Fastqsanger.gz
	SRR3471541.fastq.gz	Fastqsanger.gz
	SRR3471551.fastq.gz	Fastqsanger.gz
	SRR3471542.fastq.gz	Fastqsanger.gz

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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.

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

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ZFP281 coordinates DNMT3 and TET1 in pluripotent state transitions

Project description:ZFP281 coordinates DNMT3 and TET1 in pluripotent state transitions

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

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

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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.

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

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