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A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
Published on: May 22, 2019
Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer.
Kimiko Inoue1, Takashi Kohda, Michihiko Sugimoto
1BioResource Center, RIKEN, 305-0024 Tsukuba, Japan.
Science (New York, N.Y.)
|September 18, 2010
Summary
Scientists improved mammal cloning by identifying and correcting specific genome reprogramming errors. Deleting the Xist gene in cloned embryos significantly boosted cloning efficiency and corrected gene expression issues.
Area of Science:
- Reproductive biology
- Genetics
- Epigenetics
Background:
- Somatic cell nuclear transfer (SCNT) is a key technology for cloning mammals.
- SCNT is hampered by low efficiency due to incomplete reprogramming of the donor cell genome.
- The specific, nonrandom errors in SCNT reprogramming are not well understood.
Purpose of the Study:
- To investigate nonrandom, SCNT-specific reprogramming errors.
- To identify mechanisms causing these errors and explore strategies for improving cloning efficiency.
Main Methods:
- Analysis of cloned mouse embryos generated via SCNT.
- Investigated the expression of Xist, a noncoding RNA involved in X-chromosome inactivation.
- Utilized genetic deletion of Xist from the active X chromosome (Xa).
- Assessed global gene expression and histone modifications in cloned embryos.
Main Results:
- Ectopic expression of Xist from the active X chromosome (Xa) was observed in cloned mouse embryos of both sexes.
- Deleting Xist from the Xa in cloned embryos led to normal global gene expression.
- Deletion of Xist resulted in an eight- to ninefold increase in cloning efficiency.
- An Xist-independent mechanism involving repressive histone marks was found to down-regulate specific X-linked genes.
Conclusions:
- Identified ectopic Xist expression and Xist-independent histone modifications as nonrandom reprogramming errors in SCNT.
- Demonstrated that correcting these errors, specifically by deleting Xist from the Xa, significantly enhances cloning efficiency.
- These findings offer a pathway to improve SCNT methods for mammalian cloning.
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