"If we tried to read a book that had the letters arranged in rows, we could not understand it," says Linhart. "We not only need the letters arranged in sequence, we need spaces and formatting to separate the letters into words, sentences and paragraphs. In the same way, we can imagine the human genome as a list of letters printed one after the other, without spaces or formatting. Methylation and protein packaging of DNA help the cell 'read' and make sense of the DNA sequence, determining which genes need to be active to perform a particular function, and which ones need to be switched off."
As cells renew and divide, their characteristic methylation and packaging pattern is usually maintained and transmitted to the new cells, ensuring that recently formed heart cells, for example, carry the same correct instructions for how to behave in order to contract and pump blood.
Trouble arises, however, when there is either too little methylation throughout the DNA (hypomethylation) or too much on specific regions of the strand (hypermethylation)both of which are frequently observed in cancer. In the last decade, scientists at Whitehead Institute and elsewhere demonstrated that the first phenomenontoo little methylation throughout the genomeis causally associated with the development of cancer.
The most recent Whitehead study established a direct causal connection between the second form of methylation imbalanceregional increases in methylationand the development of colon tumors. The scientists did this by giving mice prone to developing intestinal tumors four variations of an enzyme that causes methylation. "We wanted to
|Contact: Eric Bender|
Whitehead Institute for Biomedical Research