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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

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

ORGANISM(S): Mus musculus

PROVIDER: GSE131017 | GEO | 2019/10/14

REPOSITORIES: GEO

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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2.

Project description:Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bidirectional regulator of cell state interconversion. We showed that subtle chromatin binding changes in differentiated cells translate into activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and stabilization of the zinc finger TF Zic2 at enhancers and promoters. Genetic gain-of-function and loss-of-function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state and in restricting reprogramming of EpiSCs. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity.

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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (RNA-seq)

Project description:Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bi-directional regulator of cell state interconversion. We showed that subtle chromatin occupancy changes in differentiated cells translate into binding and activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and the zinc finger TF Zic2 at enhancers and promoters. Genetic gain and loss of function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state, and in restricting EpiSC reprogramming. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity.

2019-10-14 | GSE131015 | GEO

Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (ChIP-seq)

Project description:Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bi-directional regulator of cell state interconversion. We showed that subtle chromatin occupancy changes in differentiated cells translate into binding and activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and the zinc finger TF Zic2 at enhancers and promoters. Genetic gain and loss of function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state, and in restricting EpiSC reprogramming. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity.

2019-10-14 | GSE131014 | GEO

Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

Project description:Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (ChIP-seq)

Project description:Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (ChIP-seq)

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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (RNA-seq)

Project description:Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (RNA-seq)

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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 Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States

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

2016-06-28 | GSE81045 | GEO

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.

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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