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The Hidden Key to Gene Control: Why Does Methylation Repress Gene Transcription?
In the research of molecular biology, the methylation process of DNA has received more and more attention. This biological process involves the addition of methyl groups to DNA molecules, changing the activity of the DNA fragment without changing its sequence. When methylation occurs at a gene promoter, it often inhibits gene transcription. Methylation is crucial in the normal development of mammals and is closely related to multiple key processes such as gene imprinting, X chromosome inactivation, inhibition of transposable elements, aging and carcinogenesis.
DNA methylation is one of the key regulatory mechanisms of gene expression, which is equivalent to a "switch" of gene expression to some extent.
Mechanism of action of methylation
DNA methylation affects gene transcription in two main ways. First, methylated DNA itself may physically hinder the binding of transcription proteins; second, methylated DNA can be bound by proteins called methyl-CpG binding proteins (MBDs). These MBD proteins recruit other proteins to the gene segment, such as histone deacetylase and other chromatin remodeling proteins, thereby changing the structure of histones to form a compact, inactive chromatin structure called heterochromatin.
Studies have shown that for approximately 60-70% of genes, promoters containing CpG islands remain unmethylated during transcriptional activity.
The role of CpG Island
In mammals, CpG islands of many genes are considered to be transcription-initiable sites. These CpG islands are usually longer than 200 base pairs and have a G+C content of more than 50%. Their presence makes genes less susceptible to methylation during expression, thus ensuring the stability and activity of genes.
The relationship between cancer and methylation
In the process of various diseases, CpG islands in gene promoters often appear abnormally hypermethylated, which leads to silencing of transcription, and this change can be inherited to daughter cells during cell division. Alterations in methylation are considered an important factor in the development of cancer, especially hypomethylation and hypermethylation, which have distinct effects in different types of tumors.
DNA methylation is also believed to play an important role in cardiovascular diseases such as atherosclerosis and may serve as an early biomarker to predict disease risk.
Aging and DNA methylation
In humans and other mammals, DNA methylation levels can accurately predict the age of tissues and cell types. The global loss of methylation becomes increasingly evident with age, demonstrating the stability and adaptability of DNA methylation during aging.
Exercise and gene regulation
High-intensity exercise was found to reduce DNA methylation in skeletal muscle, demonstrating the profound impact of exercise on gene regulation. Additionally, individuals who exercise chronically also show changes in methylation levels in adipose tissue.
In short, DNA methylation, as an important mechanism of gene regulation, affects multiple biological processes, from development and aging to the development of diseases. Understanding the impact of methylation on gene expression is key to future biomedical research. As our understanding of this process increases, can DNA methylation become a breakthrough for new treatments?
