Friday, November 14, 2008

Demonstration of epigenetic changes due to early stress, and how do you measure methylation?

An interesting paper showing epigenetic changes caused by early stress has recently come out in PNAS (see below). Siblings who were in utero during the Dutch Famine in the winter of '44 - '45 had less methylation on the IGF2 gene compared to their same-sex siblings who were not in utero during the famine.

So, how exactly does one measure methylation?
According to the paper, and a Wikipedia entry:
First, methylation usually occurs on CpG cytosines, and when you treat your piece of DNA with bisulfite, the methylated cytosines becomes reduced to uracil. Then a variety of PCR methods and/or sequencing methods can be applied. In this paper they use a mass-spectroscopy based method called Epityper.

Persistent epigenetic differences associated with prenatal exposure to famine in humans
Bastiaan T. Heijmansa, Elmar W. Tobia, Aryeh D. Stein, Hein Putter, Gerard J. Blauw, Ezra S. Susser, P. Eline Slagboom, and L. H. Lumeye
PNAS 2008 105:17046-17049
Abstract: Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944–45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.

No comments:

Locations of visitors to this page