Normal gene control increases chances human stem cells wi...( use only parent-of-origin controls expr...)

use only parent-of-origin controls expression of an imprinted gene, when one is passed, say, from a mother to her son to his daughter, the biochemical "mark" that identifies the gene as a maternal or a paternal copy must be removed and a new mark put on. If parental marks were lost in cultured stem cells, as some scientists had proposed was likely, both copies of the imprinted gene would be active.

"The inheritance rules Mendel observed in his pea garden aren't operating here," explains Feinberg. "'Dominant' and 'recessive' don't explain imprinted genes. Instead, for some imprinted genes, only the copy from the mother is used, while for others, only the copy from the father is turned on -- generation after generation."

Believed to be the first to study imprinting in human stem cells, Feinberg and the research team found that the primitive germ cells themselves lacked active imprinting of the four genes studied, but specialized daughter cells had appropriate expression of one copy over another.

"This makes sense," says first author Patrick Onyango, a post doctoral fellow in the McKusick-Nathans Institute, "because some genes are imprinted in the whole organism, and some only in particular tissues. It's probably efficient for a stem cell to have both copies turned on, and then reactivate imprinting to shut off one copy, depending on what type of specialized cell it becomes."

Feinberg and other researchers in the field hypothesize that imprinted genes carry "latent" marks in certain situations -- such as in pluripotent stem cells and in cancers that have both copies of an imprinted gene improperly active.

"In these instances, we've observed that an apparent loss of imprinting can be reversed, either by the cell itself or by giving a drug, in the case of cancer," says Feinberg. "So these imprinted genes, we believe, haven't completely lost the mark that says whether the copy came from mom or dad -- it's still there, it's just
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
8-Jul-2002

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