They also discovered that the abnormal expression of one particular gene, called H19, was linked to a chemical alteration in part of the gene called methylation, another epigenetic phenomenon. Methylation, the addition of methyl groups to particular DNA nucleotides, makes the gene harder to transcribe and therefore lowers its expression levels. Degrees of methylation of H19 varied between the clones.
Although most of the mice showed increased birth and placental weights, along with the changes in gene expression, the researchers didn't find any significant correlation between any of the specific variations in gene expression and increased weight. The cumulative action of many abnormally expressed genes may be necessary to produce the overgrowth in clones, say the researchers in their report.
After documenting the changes in gene expression for the clones themselves, the investigators turned their attention to a second question: were these abnormalities produced by the cloning process itself, or did they already exist in the embryonic stem cells used to create the clones?
The scientists found that variation in imprinted gene expression was rampant among the stem cells as well. Wide variation in expression was observed between different embryonic stem cell lines, between individual colonies of cells, or subclones, of each line, and even between individual cells within each colony, surprising the researchers.
This research suggests that extreme variability in gene expression may be the hallmark of embryonic stem cells, noted Jaenisch.
The researchers are interested in finding out whether the epigenetic state of human embryonic stem cells cultured fo
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Contact: Ginger Pinholster
gpinhols@aaas.org
202-326-6421
American Association for the Advancement of Science
5-Jul-2001