scholarly journals Dppa2/4 target chromatin bivalency enabling multi-lineage commitment

2019 ◽  
Author(s):  
Mélanie A. Eckersley-Maslin ◽  
Aled Parry ◽  
Marloes Blotenburg ◽  
Christel Krueger ◽  
Valar Nila Roamio Franklin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Rna Polymerase ◽  
Single Cell ◽  
Embryonic Stem ◽  
Lineage Commitment ◽  
Double Knockout ◽  
Pluripotent Cells ◽  
Low Expression

AbstractBivalent chromatin marks developmental promoters in pluripotent cells, yet their targeting and precise impact on lineage commitment remains unclear. We uncover Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as epigenetic priming factors, establishing chromatin bivalency. Single-cell transcriptomics and differentiation assays reveal Dppa2/4 double knockout embryonic stem cells fail to exit pluripotency and differentiate efficiently. Dppa2/4 associate with COMPASS and Polycomb complexes and are required to recruit and maintain their binding at a subset of developmentally important bivalent promoters which are characterised by low expression and poised RNA polymerase. Consequently, upon Dppa2/4 knockout, these dependent promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel targeting principle for bivalency to developmental promoters, poising them for future lineage specific activation.

scholarly journals Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

2016 ◽  
Author(s):  
Stefan Semrau ◽  
Johanna Goldmann ◽  
Magali Soumillon ◽  
Tarjei S. Mikkelsen ◽  
Rudolf Jaenisch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell ◽  
Embryonic Stem ◽  
Lineage Commitment ◽  
Single Cell Level ◽  
Cell Level ◽  
Expression Variability ◽  
Gene Expression Heterogeneity

ABSTRACTGene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measured the gene expression dynamics of retinoic acid driven mESC differentiation using an unbiased single-cell transcriptomics approach. We found that the exit from pluripotency marks the start of a lineage bifurcation as well as a transient phase of susceptibility to lineage specifying signals. Our study revealed several transcriptional signatures of this phase, including a sharp increase of gene expression variability. Importantly, we observed a handover between two classes of transcription factors. The early-expressed class has potential roles in lineage biasing, the late-expressed class in lineage commitment. In summary, we provide a comprehensive analysis of lineage commitment at the single cell level, a potential stepping stone to improved lineage control through timing of differentiation cues.

scholarly journals Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Stefan Semrau ◽  
Johanna E. Goldmann ◽  
Magali Soumillon ◽  
Tarjei S. Mikkelsen ◽  
Rudolf Jaenisch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell ◽  
Embryonic Stem ◽  
Lineage Commitment

scholarly journals Pooled CRISPR-activation screening coupled with single-cell RNA-seq in mouse embryonic stem cells

2021 ◽  
Vol 2 (2) ◽  
pp. 100426
Author(s):  
Celia Alda-Catalinas ◽  
Melanie A. Eckersley-Maslin ◽  
Wolf Reik
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Rna Seq ◽  
Crispr Activation

scholarly journals RNA Polymerase II-Association Factor 1 (Paf1/PD2) Maintains Self-renewal by Its Interaction with Oct3/4 in Mouse Embryonic Stem Cells

Stem Cells ◽  
2009 ◽  
pp. N/A-N/A ◽  
Author(s):  
Moorthy P. Ponnusamy ◽  
Shonali Deb ◽  
Parama Dey ◽  
Subhankar Chakraborty ◽  
Satyanarayana Rachagani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Self Renewal

scholarly journals DNA methylation on N6-adenine in mammalian embryonic stem cells

Nature ◽  
2016 ◽  
Vol 532 (7599) ◽  
pp. 329-333 ◽  
Author(s):  
Tao P. Wu ◽  
Tao Wang ◽  
Matthew G. Seetin ◽  
Yongquan Lai ◽  
Shijia Zhu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem

scholarly journals DAXX safeguards pericentromeric heterochromatin formation in embryonic stem cells

2021 ◽  
Author(s):  
Antoine Canat ◽  
Adeline Veillet ◽  
Robert Illingworth ◽  
Emmanuelle Fabre ◽  
Pierre Therizols
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Pericentric Heterochromatin ◽  
Dna Demethylation ◽  
Pericentromeric Heterochromatin ◽  
Major Satellite ◽  
Heterochromatin Formation

AbstractDNA methylation is essential for heterochromatin formation and repression of DNA repeat transcription, both of which are essential for genome integrity. Loss of DNA methylation is associated with disease, including cancer, but is also required for development. Alternative pathways to maintain heterochromatin are thus needed to limit DNA damage accumulation. Here, we find that DAXX, an H3.3 chaperone, protects pericentromeric heterochromatin and is essential for embryonic stem cells (ESCs) maintenance in the ground-state of pluripotency. Upon DNA demethylation-mediated damage, DAXX relocalizes to pericentromeric regions, and recruits PML and SETDB1, thereby promoting heterochromatin formation. In the absence of DAXX, the 3D-architecture and physical properties of pericentric heterochromatin are disrupted, resulting in derepression of major satellite DNA. Using epigenome editing tools, we demonstrate that H3.3, and specifically H3.3K9 modification, directly contribute to maintaining pericentromeric chromatin conformation. Altogether, our data reveal that DAXX and H3.3 unite DNA damage response and heterochromatin maintenance in ESCs.

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