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A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
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DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development
Yin-Li Zhang1,2, Long-Wen Zhao1, Jue Zhang1
1Life Sciences Institute, Zhejiang University, Hangzhou, China.
The EMBO Journal
|August 17, 2018
Summary
A novel protein, CRL4-DCAF13, is essential for early embryonic development by degrading SUV39H1. This process removes histone trimethylation (H3K9me3), enabling genome reprogramming in mammalian embryos.
Area of Science:
- Epigenetics and Developmental Biology
- Cellular Reprogramming
- Ubiquitin Ligase Function
Background:
- Mammalian oocytes and zygotes can reprogram somatic cells to a totipotent state.
- SUV39H1/2-mediated histone H3 lysine-9 trimethylation (H3K9me3) impedes efficient reprogramming.
- Regulation of SUV39H1/2 in early embryos and iPSC generation is not fully understood.
Purpose of the Study:
- To investigate the regulation of SUV39H1/2 during early embryonic development and iPSC generation.
- To identify novel CRL4 E3 ubiquitin ligase adaptors (DCAFs) involved in embryonic development.
Main Methods:
- Analysis of CRL4 adaptors (DCAFs) in mammalian embryos.
- Generation and analysis of Dcaf13 knockout mice.
- Assessment of embryonic development, H3K9me3 levels, and SUV39H1 polyubiquitination and degradation.
Main Results:
- DCAF13 was identified as a novel CRL4 adaptor essential for preimplantation development.
- Dcaf13 knockout embryos arrested at the eight- to sixteen-cell stage with elevated H3K9me3.
- CRL4-DCAF13 targets SUV39H1 for degradation, facilitating H3K9me3 removal and zygotic gene activation.
Conclusions:
- CRL4-DCAF13-mediated SUV39H1 degradation is crucial for genome reprogramming in early mammalian embryos.
- This pathway is vital for overcoming reprogramming barriers and enabling totipotency.
- DCAF13 plays a critical role in female fertility and embryonic development.
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