Print ArticleDr. Shirley Tilghman and colleagues (Princeton University) lend new insight into the mechanism of genomic imprinting, demonstrating a necessary role for a non-coding RNA transcript in the silencing of an imprinted gene cluster in mice.
Imprinting, or the differential expression of a gene based upon which parent it has been inherited from, is integral to normal growth and development. Two human disorders, Prader-Willi and Angelman syndromes, result from the deletion of the identical portion of chromosome 15. Imprinting determines which disorder arises: When the deletion involves the chromosome 15 that came from the father, the child has Prader-Willi syndrome, but when the deletion involves the chromosome 15 that came from the mother, the child has Angelman syndrome.
In the mouse, a cluster of nine genes on the distal end of the number 7 chromosome is imprinted. Dr. Tilghman and colleagues made a series of targeted alterations to ascertain which sequences are responsible for their paternal-specific silencing. The researchers show that this imprinted gene silencing requires the elongation of a paternally-expressed non-coding RNA transcript, Kcnq1ot1.
"As we explore the mechanism of genomic imprinting in greater detail, it is becoming clear that there is not a single explanation for the silencing of all imprinted genes. Rather mammals have co-opted multiple transcriptional regulatory mechanisms that were already evolved. In the case of the Kcnqt1ot1, the mechanism utilizes some form of RNA silencing. The variation in silencing mechanisms lends further support to the argument that imprinting arose gradually over a long period in mammals, not all at once," explains Dr. Tilghman.
Source : Cold Spring Harbor Laboratory
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