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Chinese scientists reveal the mechanism of Dcaf11 regulating telomere extension in mouse embryo development |
At 0:00 on October 24, 2020, Beijing time, a team led by Professor Gao Shaorong from the School of Life Science and Technology of Tongji University and a team led by Professor Ju Zhenyu from Jinan University published a titled "Dcaf11 activates Zscan4-mediated alternative telomere" in the Cell Stem Cell magazine.
"lengthening in early embryos and embryonic stem cells"
.
The study found that the embryonic factor Dcaf11 plays an important role in the ALT-mediated telomere extension and maintenance of mouse early embryos and embryonic stem cells
.
It reveals the key factors and the mechanism of action in the ALT process of early embryos, and provides important clues for further understanding of the ALT mechanism of early embryos
Using the dynamic map of the mouse preimplantation embryo proteome drawn by the research team in the early stage, the team members further screened the potential ALT-related genes in the early embryo in embryonic stem cells, and discovered a series of factors that affect the ALT process of the early embryo Among them, Dcaf11 is the most obvious in promoting the activation of ALT of embryonic stem cells
.
Then the researchers constructed Dcaf11 knockout mice and analyzed the role of Dcaf11 in mouse embryonic development
.
The results showed that the deletion of Dcaf11 would cause a decrease in mouse preimplantation embryo development rate, abnormal gene expression, and a decrease in telomere extension rate during cleavage stage embryos
Figure 1: The effect of Dcaf11 on Zscan4 activation, embryonic development, and telomere elongation and maintenance
In addition, with the increase of the generation of Dcaf11 knockout mice, the telomeres of Dcaf11 knockout mice gradually shortened
.
The hematopoietic reconstitution ability of bone marrow hematopoietic stem cells in late generation Dcaf11 knockout mice and their ability to repair damage under stress decreased significantly
Figure 2: Dcaf11 knockout mouse bone marrow hematopoietic stem cells have a significant decrease in hematopoietic reconstruction ability and damage repair ability under stress
Next, the researchers explored the mechanism by which Dcaf11 promotes telomere lengthening
.
The researchers discovered that Dcaf11 acts as an E3 ubiquitin ligase recognition protein, targets the substrate Kap1 and promotes its degradation
The researchers further found that Kap1 can bind to the downstream enhancer of Zscan4 and inhibit the activation of Zscan4 by maintaining the H3K9me3 modification there
.
When DCaf11 is overexpressed in cells, Kap1 bound to the Zscan4 enhancer is degraded, Zscan4 is activated, and telomere lengthening is promoted
In summary, this study reveals the mechanism of Dcaf11 in early embryonic ALT-mediated telomere extension, and provides important clues for further understanding of early embryonic telomere extension and regulatory mechanisms
.
Assistant Professor Le Rongrong of Tongji University Gao Shaorong's research group, Ph.
D.
student Huang Yixin, assistant researcher Zhang Yanping, Professor Wang Hu of Ju Zhenyu's research group of Jinan University, and Lin Jiaming, a master student of Gao Shaorong's research group of Tongji University are the co-first authors of the paper.
The professor and Assistant Professor Le Rongrong are the co-corresponding authors
.
The research was supported by the key R&D program of the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Shanghai Science and Technology Commission
.
(Source: Science Net)
Related paper information: https://doi.
https://doi.
org/10.
1016/j.
stem.
2020.
11.
018 https://doi.
org/10.
1016/j.
stem.
2020.
11.
018