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The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation

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

ORGANISM(S): Mus musculus

PROVIDER: GSE93044 | GEO | 2017/11/24

SECONDARY ACCESSION(S): PRJNA359643

REPOSITORIES: GEO

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The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation [RNA-seq]

Project description:The early development of mouse embryos involves a tightly regulated series of lineage specification events. Following implantation, these events include maturation of the pluripotent epiblast and simultaneous establishment of the embryonic axes. Here we report that Zfp281, a transcription factor shown to be required for transitioning cells in culture from naïve to primed states of pluripotency, is essential for mouse embryonic development by regulating epiblast maturation. Transcriptomic analyses of Zfp281 mutant embryos revealed a failure in activating Nodal signaling in the epiblast leading to failure in establishing the anterior-posterior axis, and impaired epiblast maturation. Our study establishes Zfp281 as a critical factor that coordinates transcriptional and epigenetic control of pluripotent epiblast maturation.

2017-11-24 | GSE93043 | GEO

The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation [ChIP-seq]

2017-11-24 | GSE93042 | GEO

Zfp281 is essential for mouse epiblast maturation through transcriptional and epigenetic control of Nodal signaling.

Project description:Pluripotency is defined by a cell's potential to differentiate into any somatic cell type. How pluripotency is transited during embryo implantation, followed by cell lineage specification and establishment of the basic body plan, is poorly understood. Here we report the transcription factor Zfp281 functions in the exit from naive pluripotency occurring coincident with pre-to-post-implantation mouse embryonic development. By characterizing Zfp281 mutant phenotypes and identifying Zfp281 gene targets and protein partners in developing embryos and cultured pluripotent stem cells, we establish critical roles for Zfp281 in activating components of the Nodal signaling pathway and lineage-specific genes. Mechanistically, Zfp281 cooperates with histone acetylation and methylation complexes at target gene enhancers and promoters to exert transcriptional activation and repression, as well as epigenetic control of epiblast maturation leading up to anterior-posterior axis specification. Our study provides a comprehensive molecular model for understanding pluripotent state progressions in vivo during mammalian embryonic development.

| S-EPMC5708896 | biostudies-literature

The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation

Project description:The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation

| PRJNA359643 | 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 is essential for epiblast maturation through a cell autonomous effect.

Project description: Not available

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Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming.

Project description:Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage-specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for the core pluripotency factors Oct4, Sox2, and Nanog. In this study, we sought to dissect the molecular control mechanism of SE activity in pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, we identified Tex10 as a key pluripotency factor that plays a functionally significant role in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation at SEs. Tex10 activity is also important for pluripotency and reprogramming in human cells. Our study therefore highlights Tex10 as a core component of the pluripotency network and sheds light on its role in epigenetic control of SE activity for cell fate determination.

| S-EPMC4458159 | biostudies-literature

Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming

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

2015-05-06 | E-GEOD-66736 | biostudies-arrayexpress

Epigenetic control of transcriptional regulation in pluripotency and early differentiation.

Project description:Pluripotent stem cells give rise to all cells of the adult organism, making them an invaluable tool in regenerative medicine. In response to differentiation cues, they can activate markedly distinct lineage-specific gene networks while turning off or rewiring pluripotency networks. Recent innovations in chromatin and nuclear structure analyses combined with classical genetics have led to novel insights into the transcriptional and epigenetic mechanisms underlying these networks. Here, we review these findings in relation to their impact on the maintenance of and exit from pluripotency and highlight the many factors that drive these processes, including histone modifying enzymes, DNA methylation and demethylation, nucleosome remodeling complexes and transcription factor-mediated enhancer switching.

| S-EPMC6803368 | biostudies-literature

Zfp281 functions as a transcriptional repressor for pluripotency of mouse embryonic stem cells.

Project description:Embryonic stem cells (ESCs) derived from preimplantation blastocysts have unique self-renewal and multilineage differentiation properties that are controlled by key components of a core regulatory network including Oct4, Sox2, and Nanog. Understanding molecular underpinnings of these properties requires identification and characterization of additional factors that act in conjunction with these key factors in ESCs. We have previously identified Zfp281, a Krüppel-like zinc finger transcription factor, as an interaction partner of Nanog. We now present detailed functional analyses of Zfp281 using a genetically ablated null allele in mouse ESCs. Our data show that while Zfp281 is dispensable for establishment and maintenance of ESCs, it is required for their proper differentiation in vitro. We performed microarray profiling in combination with previously published datasets of Zfp281 global target gene occupancy and found that Zfp281 mainly functions as a repressor to restrict expression of many stem cell pluripotency genes. In particular, we demonstrated that deletion of Zfp281 resulted in upregulation of Nanog at both the transcript and protein levels with concomitant compromised differentiation of ESCs during embryoid body culture. Chromatin immunoprecipitation experiments demonstrated that Zfp281 is required for Nanog binding to its own promoter, suggesting that Nanog-associated repressive complex(es) involving Zfp281 may fine-tune Nanog expression for pluripotency of ESCs.

| S-EPMC3272666 | biostudies-literature

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