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An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
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YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation
Fabiana Passaro1, Ilaria De Martino1, Federico Zambelli2
1Department of Molecular Medicine and Medical Biotechnology, University of Napoli Federico II, Italy.
The Journal of Biological Chemistry
|December 3, 2020
Summary
Transiently reducing Yes-associated protein (YAP) in mouse embryonic stem cells (ESCs) disrupts cellular homeostasis and proper differentiation. This YAP downregulation alters genome-wide DNA methylation, impacting ESCs
Area of Science:
- Cell Biology
- Epigenetics
- Developmental Biology
Background:
- The Yes-associated protein (YAP) is a key effector of the Hippo pathway, regulating cellular processes like proliferation and morphogenesis.
- YAP interacts with transcription factors and epigenetic complexes, influencing gene expression.
- Its role in embryonic stem cell (ESC) stemness and differentiation remains under investigation.
Purpose of the Study:
- To investigate the role of YAP in mouse ESC differentiation and pluripotency.
- To elucidate the molecular mechanisms underlying YAP's influence on ESC fate.
- To identify potential epigenetic regulators affected by YAP modulation.
Main Methods:
- Transient knockdown of YAP in mouse ESCs.
- Bisulfite genomic sequencing to analyze DNA methylation patterns.
- Gene expression analysis to identify key regulatory molecules.
Main Results:
- Transient YAP downregulation in mouse ESCs impairs proper differentiation and cellular homeostasis.
- This perturbation leads to genome-wide alterations in DNA methylation remodeling during early differentiation.
- Upregulation of the long noncoding RNA ephemeron and Dnmt3l were identified as potentially involved in the altered methylation profile.
Conclusions:
- YAP plays a critical role in maintaining epigenetic dynamics during ESC exit from pluripotency.
- YAP influences DNA methylation remodeling essential for proper differentiation.
- Ephemeron and Dnmt3l may mediate YAP's effects on epigenetic regulation in ESCs.
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