Related Experiment Videos
Delta-crystallin genes become hypomethylated in postmitotic lens cells during chicken development
Abstract:
Although it has been argued that the loss of 5-methylcytosine from specific sites in DNA plays an important role in activation of specific genes, the mechanism of hypomethylation is not well understood. One model links the process to DNA replication, proposing that it occurs by not remethylating cytosine on newly synthesized DNA. An alternative model argues that hypomethylation results from excision of part or all of the 5-methylcytosine. We were able to test whether hypomethylation can occur without replication by analysis of methylation changes in the delta-crystallin genes of the chicken lens. During embryonic development a large fraction of cells in the lens stops dividing as part of the differentiation process. Shortly after this stage, the delta-crystallin genes in samples of the whole lens become hypomethylated, suggesting the possibility that this process might be occurring in the subset of cells that is no longer dividing. We found that hypomethylation of these genes does occur in postmitotic lens cells, a result that implicates an excision mechanism in this tissue.
Insights
DNA hypomethylation, the loss of 5-methylcytosine, can occur without cell division. This study suggests an excision mechanism, not just replication-dependent dilution, is involved in gene activation.
Area of Science:
- Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- The role of DNA hypomethylation in gene activation is established, but the underlying mechanisms remain unclear.
- Two models exist: replication-dependent dilution and excision of 5-methylcytosine.
Purpose of the Study:
- To investigate whether DNA hypomethylation can occur independently of DNA replication.
- To determine the mechanism of hypomethylation in postmitotic cells.
Main Methods:
- Analysis of methylation changes in chicken lens delta-crystallin genes during embryonic development.
- Studying methylation in postmitotic (non-dividing) lens cells.
Main Results:
- Hypomethylation of delta-crystallin genes was observed in the chicken lens shortly after cells cease dividing.
- This hypomethylation occurs in postmitotic cells, indicating it does not require DNA replication.
Conclusions:
- DNA hypomethylation can occur in the absence of DNA replication.
- The findings implicate an excision mechanism for DNA hypomethylation in postmitotic lens cells.