What is CpG island methylation?
CpG sites occur with high frequency in genomic regions called CpG islands (or CG islands). Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosines. Enzymes that add a methyl group are called DNA methyltransferases. In mammals, 70% to 80% of CpG cytosines are methylated.
What are CpG islands in genetics?
CpG islands are DNA methylations regions in promoters known to regulate gene expression through transcriptional silencing of the corresponding gene. DNA methylation at CpG islands is crucial for gene expression and tissue-specific processes.
What is CpG methylation used for?
Silencing of DNA repair genes through methylation of CpG islands in their promoters appears to be especially important in progression to cancer (see methylation of DNA repair genes in cancer).
Do CpG islands get methylated?
It is estimated that in mammalian genomes about 80% of CpG dinucleotides are methylated. However, CpG dinucleotides in regions abundant in GC pairs, such as CpG clusters and CpG islands (CGIs), are usually unmethylated, and this is an important feature of gene promoters and gene expression control [33].
What causes CpG island methylation?
The reason for methylation to be almost exclusive to CpG dinucleotides is the symmetry of the dinucleotide. This allows for preservation during cell division and is a hallmark for epigenetic modifications.
How is CpG methylation detected?
Currently, there are three primary methods to identify and quantify DNA methylation. These are: sodium bisulfite conversion and sequencing, differential enzymatic cleavage of DNA, and affinity capture of methylated DNA (1). Restriction enzyme based differential cleavage of methylated DNA is locus-specific.
How many CpG islands are there?
30,000 CpG islands
The human genome contains ∼30,000 CpG islands (CGIs), long stretches (0.5–2 kb) of DNA with unusually elevated levels of CpG dinucleotides. Many occur at genes’ promoters, and their DNA nearly always remains unmethylated.
How is CPG methylation detected?
Does methylation increase gene expression?
Evidence suggests that DNA methylation of the gene body is associated with a higher level of gene expression in dividing cells (Hellman and Chess, 2007; Ball et al, 2009; Aran et al, 2011).
How do you check methylation status?
What is the CpG island methylator phenotype ( CIMP )?
The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci.
When was CpG island hypermethylation discovered in humans?
History. The first discovery of methylation in a CpG island of a tumor suppressor gene in humans was that of the Retinoblastoma (Rb) gene in 1989. This was just a few years after the first oncogene mutation was discovered in a human primary tumor. The discovery of the methylation-associated inactivation of the Von Hippel-Lindau (VHL)…
How is CpG island related to tumor suppressor genes?
The association of transcriptional silencing of tumor suppressor genes with hypermethylation is the foundation upon which this subset of cancer epigenetics stands. In a normal cell, the CpG island is hypomethylated, and the rest of the genome is methylated.
Why is DNA methylation almost exclusive to CpG dinucleotides?
In mammals, DNA methylation occurs almost exclusively at cytosine chains that are followed by guanine. The reason for methylation to be almost exclusive to CpG dinucleotides is the symmetry of the dinucleotide. This allows for preservation during cell division and is a hallmark for epigenetic modifications.
