Imprecise DNMT1 activity coupled with neighbor-guided correction enables robust yet flexible epigenetic inheritance
| Autor: | Yu Zhang, Weikun Xia, Chunyi Huang, Yuanyuan Li, Bing Zhu, Wen-Hao Zhang, Xiguang Xu, Hehuang Xie, Wei Xie, Guang Yu, Qiujun Wang, Xuan Ming |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Epigenomics Heredity Computational biology Biology Epigenesis Genetic 03 medical and health sciences Mice 0302 clinical medicine Databases Genetic Genetics Animals Epigenetics Mitosis Cells Cultured 030304 developmental biology Epigenesis 0303 health sciences Mechanism (biology) Epigenome DNA DNA Methylation CpG site DNA methylation DNMT1 CpG Islands 030217 neurology & neurosurgery |
| Zdroj: | Nature genetics. 52(8) |
| ISSN: | 1546-1718 |
| Popis: | The epigenome, including DNA methylation, is stably propagated during mitotic division. However, single-cell clonal expansion produces heterogeneous methylomes, thus raising the question of how the DNA methylome remains stable despite constant epigenetic drift. Here, we report that a clonal population of DNA (cytosine-5)-methyltransferase 1 (DNMT1)-only cells produces a heterogeneous methylome, which is robustly propagated on cell expansion and differentiation. Our data show that DNMT1 has imprecise maintenance activity and possibly possesses weak de novo activity, leading to spontaneous 'epimutations'. However, these epimutations tend to be corrected through a neighbor-guided mechanism, which is likely to be enabled by the environment-sensitive de novo activity ('tuner') and maintenance activity ('stabilizer') of DNMT1. By generating base-resolution maps of de novo and maintenance activities, we find that H3K9me2/3-marked regions show enhanced de novo activity, and CpG islands have both poor maintenance and de novo activities. The imprecise epigenetic machinery coupled with neighbor-guided correction may be a fundamental mechanism underlying robust yet flexible epigenetic inheritance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink