mandag den 13. august 2018

Functions of DNA methylation

Functions of DNA methylation
Abstract (ref 1):
DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.

The effects of variations in CpG methylation on coding genes depend on the location
Quote (from ref 2, page 10):
The effects of variations in CpG methylation on coding genes depend on the location of the
differential methylation in relation to the gene of interest. There are two genic regions where the
relationship between CpG methylation and gene expression are generally well understood.
Increased CpG methylation in the TSS of genes tends to lead to a decrease in transcription either
due to the prevention of transcription factors from recognizing and binding to the promoter region for the initiation of transcription, or due to the recruitment of other methyl-binding
proteins and co-repressors [19, 56, 57]. On the other hand, increased CpG methylation in the
gene body is positively correlated with transcription [58]. Although the exact reasons are
unclear, gene body methylation is believed to be important for silencing repetitive elements,
retrotransposons, and regulating alternative splicing events [52]. (references are in ref 2)

1) Peter A. Jones: Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Revet Genet, 2012, 13, 7.

2) de Vega: 
DNA Methylation Modifications Associated with Glucocorticoid Sensitivity and Clinical Subtypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

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