On July 20, school of Life, Tsinghua University published a research paper entitled imPRECISE DNMT1 Activity coupled with nent-guided correction enabling robust yet Flexible epigenetic inheritance in the form of a long paper, which clarified the basic mechanism of how epigenetic modification can maintain stable inheritance under the action of an imprecise maintenance mechanism.This important study found that inaccurate DNMT1 methylation activity can lead to random DNA methylation epimutations.However, these epigenetic mutations tend to repair themselves during cell passage.

During the process of cell division and replication, genomic information is transmitted to the daughter cells, and epigenetic modification information is transmitted to the daughter cells to maintain the state of the cell.Unlike genomes, epigenetic transfer between generations is imprecise but stable, and highly malleable, able to adapt to and maintain different initial epigenetic states.These properties allow the epigenome to change in response to changes in a cell's fate and ultimately help maintain a cell's specific state.However, how stable epigenetic transmission is achieved is still poorly understood.

The researchers established a "DNMT1-only" mouse embryonic stem cell line and found that DNA methylation in dnMT1-only single-cell clone population cells still showed intracellular heterogeneity.At the same time, the methylation group could still be transferred stably during cell amplification and differentiation.Studies have shown that DNMT1 has imprecise methylation maintenance activity and low DE novo methylation activity, resulting in spontaneous epigenetic mutation.These epigenetic mutations tend to be repaired by a modification mechanism that is sensitive to the methylation level in adjacent regions during cell amplification.DNMT1's adjacent region sensitive DE novo methylation activity and methylation maintenance activity play an important role in this neighboring region methylation level dependent correction system.The simulation results and the genome-wide single base resolution map of DE novo methylation and maintenance activity further confirmed that DE novo methylation activity of DNMT1 was correlated with the methylation level of adjacent regions.Finally, the researchers found that different regions of the genome had different DNMT1 DE novo methylation and maintenance activities.

To sum up, this work systematically studies how epigenetic modification can achieve stable and plastic inheritance in an imprecise genetic mode, and finds new mechanisms for correction of epigenetic dependence in adjacent regions, providing new ideas for understanding epigenetic modification inheritance and the maintenance mechanism of DNA methylation on different regulatory elements.

Time:2020.07.22.

Source: https://news.tsinghua.edu.cn/info/1007/80668.htm