The ends of chromosomes are protected by specific DNA sequences called telomeres (in red). Some chromosomes are depleted of telomeres, which can result in abnormal cell division and cancer. Image credit: Thomas Ried, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health (CC BY-NC 2.0)
Genes are the instruction manuals of life and contain the information needed to build the building blocks that keep cells alive. To read these instructions, cells use specific signals that activate genes. The process, known as gene expression, is tightly controlled and for the most part, fairly stable. But gene expression can be modified in various ways.
Epigenetics is a broad term for describing reversible changes made to genes to switch them on and off. Sometimes, certain genes even develop a kind of ‘transcriptional memory’ where over time, their expression is enhanced and speeds up with repeated activation signals. But this may also have harmful effects.
For example, the signalling molecule called tumour necrosis factor α (TNF-α) is an essential part of the immune system. But it is also implicated in chronic inflammatory diseases, such as rheumatoid arthritis. In these conditions, cell signalling pathways triggering inflammation are overactive. One possibility is that TNF-α could be inducing the transcriptional memory of certain genes, amplifying their expression. But little is known about which fraction of genes exhibits transcriptional memory, and what differentiates memory genes from genes with stable expression.
Here, Zhao et al. treated cells grown in the laboratory with TNF-α to investigate its role in transcriptional memory and find out what epigenetic features might govern the process. The experiments showed that mimicking a sustained inflammation by stimulating TNF-α, triggered a transcriptional memory in some genes, and enabled them to respond to much lower levels of TNF-α on subsequent exposure.
Zhao et al. also discovered that genes tagged with methyl groups are more likely to show transcriptional memory when stimulated by TNF-α. However, they also found that these groups must be removed to consolidate any transcriptional memory.
This work shows how TNF-α influences can alter the expression of certain genes. It also suggests that transcriptional memory, stimulated by TNF-α, may be a possible mechanism underlying chronic inflammatory conditions. This could help future research in identifying more genes with transcriptional memory.
