In this study, the UCLA team found that the DNA wrapped around nucleosomes is more highly methylated than flanking DNA, which links adjacent DNA/nucleosome complexes.
"These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransfereases (the enzymes that methylates DNA) preferentially target nucloesome-bound DNA," said Pellegrini, an associate professor of molecular, cell and developmental biology and an informatics expert.
The work was initially done in Arabidopsis, a mustard weed commonly used in plant research. Once the DNA methylation and nucleosome positioning patterns emerged, they repeated the work in human stem cells. Pellegrini and Jacobsen found similar patterns in the human stem cells.
One of the most important, unknown aspects of DNA methylation, Jacobsen said, is how the cell determines where the event occurs, and the pattern of nucleosome positions has emerged as an important determinant of methylation.
The findings could have implications in fighting cancer because DNA methylation patterns go awry in cancer, often causing tumor suppressor genes to switch off. The more scientists know about the cellular mechanisms that lay down the correct DNA methylation patterns, the more that process can be manipulated. In the future, this type of research may lead to techniques that result in the ability to control the patterns that go awry and lead to cancer, thus preventing a malignancy.
And because DNA methylation is important in stem cell differentiation, this knowledge could lead to ways to correct defects in stem cells lines in the future.
|Contact: Kim Irwin|
University of California - Los Angeles