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Decrease in DNA methylase activity during preimplantation development in the mouse
Abstract:
During early mouse development, there are large-scale changes in DNA methylation. These changes may be due to the availability or stability of the enzyme, DNA methyltransferase (methylase), which is responsible for maintenance of DNA methylation. A microassay for methylase activity in preimplantation embryos shows that the level of maternally inherited enzyme is extremely high in the egg and that this activity is stable for the first three cleavage divisions. However, from the 8-cell to the blastocyst stage, there is a marked and absolute decrease in enzyme activity.
Insights
Early mouse development involves significant DNA methylation changes. A microassay revealed high maternal DNA methyltransferase activity in eggs, stable through early divisions, but sharply declining by the blastocyst stage.
Area of Science:
- Developmental Biology
- Epigenetics
- Molecular Biology
Background:
- Early mouse development is characterized by dynamic alterations in DNA methylation patterns.
- DNA methyltransferase (methylase) activity is crucial for maintaining these methylation patterns.
- Understanding the temporal regulation of methylase is key to deciphering developmental epigenetic reprogramming.
Purpose of the Study:
- To investigate the activity levels of DNA methyltransferase during preimplantation mouse development.
- To determine the stability and source of methylase activity in early embryos.
Main Methods:
- A sensitive microassay was employed to quantify methylase activity.
- Enzyme activity was measured in mouse eggs and embryos at various cleavage stages (up to blastocyst).
Main Results:
- Maternally inherited DNA methyltransferase activity was found to be exceptionally high in the unfertilized egg.
- This high enzyme activity remained stable through the first three cell divisions.
- A significant and complete reduction in methylase activity was observed between the 8-cell stage and the blastocyst stage.
Conclusions:
- The maternal DNA methyltransferase enzyme is present at high levels and is stable during the initial stages of mouse embryogenesis.
- A critical decrease in DNA methyltransferase activity occurs during the transition from the 8-cell stage to the blastocyst stage, potentially influencing large-scale epigenetic changes.