Whether it’s making the monumental move to high school, switching jobs or experiencing the culture shock from moving countries, adjusting to a new environment isn’t always easy. Often we have to make concessions and tradeoffs, the extent of which is very much dependent on the type of environment we find ourselves in. It turns out that just like the unseasoned traveller, mammalian cells also need to make an adjustment to fit in when making the move to cell culture.
Recent findings have hinted epigenetic reprogramming in transformed culture cells; however, the degree and pace at which such gain or loss of DNA methylation occurs has not been fully deciphered.
Epigenetic modifications such as DNA methylation modulate chromosomal stability and gene expression without altering DNA sequence. Having previously discovered discrepancies in levels of 5’-hydroxymethylcytosine (5hmC) between transformed cells in culture and cells from the native tissue, Nestor and colleagues decided to explore how changes to the methylome occur during the transition from primary cell to transformed cell. To satisfy their curiosity, the team explored the effects of culture exposure on the methylome, hydroxymethylome, and transcriptome of mouse embryonic fibroblasts (MEFs) in a time-dependent fashion, using numerous 5hmC and 5’-methylcytosine (5mC) analysis techniques followed by expression microarray analysis.
Here is the summary of their findings on how mammalian cells get acquainted to culture systems:
- Mammalian cells in culture undergo rapid global loss of 5hmC, but not 5mC.
- Expression of Tet1 decreases upon cell exposure to culture.
- Loss of 5hmC in culture occurs independent of 5mC levels.
- Loss of demethylase activity leads to gain of 5mC, but not 5hmC at gene promoters.
- Culture-induced changes in 5hmC levels drastically alter the transcriptome of transformed cells.
- Culture adaptation is characteristically marked with global redistribution of 5hmC.
“The implications of our work is that the Tet enzymes act as a part of a barrier against aberrant methylation in normal cells, at its most extreme the DNA modification changes that occur in cultured cells are linked to cellular transformation but do not necessarily drive it,” said Dr. Richard Meehan, the corresponding author of the study.