The Role of Methylation in Gene Expression

There are several methods of controlling gene expression in eukaryotes, of which methylation is one. This is a tool in epigenetics that allows cells to "turn off" genes. Epigenetics is the control of genes by factors not related to an individual's DNA sequence. These types of tools determine what proteins are ultimately translated and function. Preserving chromosome stability, genomic imprinting, and embryonic development all involve DNA methylation, and errors in methylation have been linked to several serious human diseases. Early experiments with 5-azacytidine, which inhibits DNA methyltransferase enzymes, allowed scientists to investigate how DNA methylation impacts cell differentiation and gene expression.


DNA methyltransferase enzymes convert the cytosine bases of eukaryotic DNA to 5-methylcytosine. This cytosine is located next to a guanine nucleotide. DNA methylation's exact role in gene expression is currently unknown, although it is possible that it blocks promoters to which transcription factors would otherwise bind. Methylation of promoters has been linked to low or no transcription. There are differences in methylation levels in different tissue types as well as between normal and cancerous cells. 


Histone methylation patterns have been found to change dramatically through the cell cycle. Some studies have shown that DNA and histone methylation are connected, such as in studies that show DNA and histone  methylation working together to ensure that proper methylation patterns are passed on to daughter cells during translation. Sometimes, when DNA is methylated, deacetylation occurs in nearby histones. This allows for a stronger inhibition of transcription. Similarly, DNA that is not methylated does not attract deacetylation enzymes to nearby histone proteins. Methylation is generally a long-term process, but it can also allow for "epigenetic reprogramming".





Research is currently being conducted into the connection between methylation errors and diseases, including lupus, cancer, and muscular dystrophy. Tumor suppressor genes have been found to be silenced in cancer cells due to hypermethylation. Overall, methylation rates in cancer cells are much higher than in normal cells. In certain cancers, hypermethylation can be a marker for diagnosing cancer, as it may be detectable in early stages of the cancers.


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