DNA Methylation and Cancer - Garvan Institute

despite the huge variation in structure and function all our cells contain the same DNA sequence the reason is that different cells use or Express only certain genes DNA can be tagged by tiny chemicals that modify gene expression one of these epigenetic modifications is DNA methylation promoter DNA methylation is associated with gene silencing and plays an important role in maintaining cell types in cancer DNA methylation patterns are altered and disrupted DNA methylation is carried out by a group of enzymes known as DNA methyl transferases or dnmt for short we have three major types dnmt1 dnmt3a and dnmt3b let's have a closer look at how they work here we are looking at an early embryonic cell and we are pulling out its DNA which are wrapped around histone octomus known as nucleosomes following fertilization dnmt3a and dnmt3b are responsible for denovo methylation allowing embryonic cells to differentiate into a cell type so for example this embryonic cell has become a distinct cell type a skin cell dnmt1 is responsible for the maintenance of DNA methylation following differentiation and is active during cell division thereafter the methylation patterns of each cell type is different and this reflects the gene expression pattern of the cell so in this case we have one skin cell becoming many skin cells this cell type has a unique methylation pattern and therefore it expresses certain genes cytosine guanine sites or cpg sites for short are found all over our DNA for example here we have a cpg island containing many cpg sites in a normal adult cell most cpg sites are methylated except in promoter cpg Islands these cpg sites are typically unmethylated promoter regions are regions in the DNA a that contain regulatory elements that control transcription of genes to understand how cpg sites are methylated let us zoom into this cytosine nucleotide here and look at its chemical structure dnmt3a and dnmt3b are responsible for DNA methylation in early development dnmt obtains the mythy group from a molecule called Sam the methyl group is added here forming five methyl cytosine it is thought that dnmt flips the cine base pair 180° out of the Strand like so then the dnmt enzyme obtains the methyl group from Sam and transfers it to the cytosine finally the methylated cytosine is flipped back human tet which stands for human 101 translocation is another important enzyme that has a role in regulating DNA methylation patterns Ted is responsible for adding a hydroxy group initially to five methylcytosine forming five hydroxymethylcytosine the Ted enzyme is also able to convert five hydroxymethyl cytosine back to cytosine through several Pathways therefore the Tet enzymes are thought to be responsible for DNA demethylation in a normal cell the two opposing processes of methylation and demethylation are tightly regulated in development however in cancer this balance is potentially disrupted and as a consequence DNA methylation patterns change typically in cancer cells we see hypermethylation of promoter cpg islands and this is associated with tumor suppressor Gene inactivation in contrast to the focal regions of hypermethylation cancer DNA also undergos widespread hypomethylation across the entire genome this bimodal deregulation of the epigenetic landscape is found in every type of human tumor critically we can now use the alteration in the methylation pattern to help us detect cancer cells from normal cells

Channel: Garvan Institute of Medical Research

Views: 213,761

Keywords: DNA Methylation, epigenetics, cancer, DNA, methylation

Id: W-S84J4zK9E

Length: 5min 16sec (316 seconds)

Published: Thu Nov 12 2015