A CpG site is a specific sequence in DNA where a cytosine (C) is followed by a guanine (G), connected by a phosphate bond. These sites play a crucial role in gene regulation and epigenetics, especially through a process called DNA methylation.
Although they might look similar to GC base pairs, CpG sites are distinct. They refer to the linear arrangement of cytosine and guanine on a single strand of DNA, not to the base pairing between strands. This sites are hotspots for chemical modifications that influence whether a gene is active or silent.
Biological role
CpG sites are found throughout the genome, but they’re particularly important when located in promoter regions, the areas that control whether a gene is turned on or off.
These sites can undergo methylation, a chemical process where a methyl group (CH₃) is added to the cytosine. When they are methylated, gene activity is often reduced or completely silenced. When unmethylated, genes are more likely to be expressed.
Through this mechanism, they play a major role in:
- Gene expression regulation;
- Cell differentiation and development;
- Response to environmental signals;
- Long term cellular memory.
CpG islands
CpG islands are regions of DNA with a high density of their sites. They are typically found near the transcription start sites of genes, particularly those involved in housekeeping and regulatory functions.
These islands are often unmethylated in healthy cells, allowing genes to remain active. However, aberrant methylation of CpG islands can lead to inappropriate gene silencing, which is a common feature in aging, inflammation and diseases like cancer.
Characteristics include:
- Length of at least 200 base pairs;
- GC content of over 50%;
- An observed to expected CpG ratio greater than 0.6.
Their role in maintaining gene expression makes CpG islands key elements in epigenetic stability and cellular health.
CpG methylation and gene expression
The methylation of CpG sites is one of the best studied epigenetic modifications. It influences gene expression without altering the underlying DNA sequence.
- When CpG sites in a promoter are methylated, the gene is usually turned off;
- When they are unmethylated, the gene is often active and expressed;
- It helps define cell identity and maintain tissue specific gene patterns.
Enzymes called DNA methyltransferases (DNMTs) are responsible for adding methyl groups to CpG sites. This process is essential for development, but also tightly linked to aging and disease when regulation is lost.
CpG and aging
One of the most consistent findings in aging research is that methylation patterns at CpG sites change over time. These changes are not random, they follow a pattern that reflects the biological age of the individual.
- Some of this sites become hypermethylated with age, silencing important genes;
- Others become hypomethylated, potentially leading to inflammation or genomic instability;
- These shifts are associated with inflammaging, mitochondrial dysfunction and cellular senescence.
This makes CpG methylation a powerful biomarker of aging and a target for interventions that aim to slow or reverse aspects of the aging process.
CpG sites are small but powerful components of the genome that influence how genes are expressed, how cells age and how we respond to our environment. Through DNA methylation, this sites act as molecular switches, shaping health outcomes across the lifespan.
Their central role in epigenetics, aging and disease prevention makes them a valuable focus for anyone interested in optimizing longevity and cellular health.
