Newly-discovered mechanism can explain the Beckwith-Wiedemann syndrome

October 24, 2008

Researchers from Uppsala University have discovered a mechanism that silences several genes in a chromosome domain. The findings, published in today's on-line issue of Molecular Cell, have implications in understanding the human disorder Beckwith-Wiedemann syndrome.

In mammals the cells contain two copies of each chromosome, one inherited from the mother and one from the father. The genes on the chromosomes can either be active or inactive. If a gene is active on the maternal chromosome, the corresponding gene is usually active also on paternal chromosome.

However, in some domains of the chromosome the activity is shut down on one of the chromosomes but not on the other. The genes in these domains cannot be activated the normal way but are completely silenced. The present study shows for the first time how this silencing of several genes on a chromosome is accomplished.

The research group, led by Chandrasekhar Kanduri, has studied a domain with several silenced genes on chromosome 7 in the mouse. The corresponding domain with silenced genes is located on the human chromosome 11. When part of this domain is transcribed a long RNA molecule, Kcnq1ot1-RNA, is formed. This RNA does not give rise to any protein, instead it mediates the silencing of eight to ten genes in a much larger area on the chromosome. Based on their findings the researchers have suggested a model for how this is accomplished. The Kcnq1ot1-RNA binds to the DNA in the domain and recruits specific enzymes that chemically modify DNA-binding proteins. This modification makes the DNA inaccessible for transcription and thereby the genes cannot be activated. In addition, the Kcnq1ot1-RNA targets the silenced domain to a specific area in the cell nucleus. There it is protected during cell division and the genes will stay silenced also in the daughter cells.

– We show for the first time how a long RNA molecule can establish and maintain silencing of multiple genes in a large domain on the chromosome, says Chandrasekhar Kanduri. The popular belief is that it is only a gene located in the same area as where the long RNA molecule is transcribed from that can be silenced.

This mechanism is important for understanding the genetic disorder Beckwith-Wiedemann Syndrome. In this condition silencing of the chromosome 11 domain does not function properly and both copies of the genes in the domain become inactive, instead of just one. Less protein is produced from the genes, leading to the excess growth characteristics associated with the syndrome: enlargement of organs in the foetus and an increased risk for tumours in the affected organs.

Source: Uppsala University

Explore further: Preventing chromosomal chaos: Protein-based genome-stabilizing mechanism discovered

Related Stories

Chromosome-folding theory shows promise

April 28, 2015

Human chromosomes are much bigger and more complex than proteins, but like proteins, they appear to fold and unfold in an orderly process as they carry out their functions in cells.

Special chromosomal structures control key genes

October 9, 2014

Within almost every human cell is a nucleus six microns in diameter—about one 300th of a human hair's width—that is filled with roughly three meters of DNA. As the instructions for all cell processes, the DNA must be ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.