Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Regulating human X chromosomes doesn’t use same gene as in mouse

01.08.2002


A gene thought to keep a single X chromosome turned on in mice plays no such role in humans, Johns Hopkins researchers report in the August issue of the American Journal of Human Genetics.



The finding is likely to relegate the disproven gene to relative obscurity, at least in humans, says Barbara Migeon, M.D., of the McKusick-Nathans Institute of Genetic Medicine, whose laboratory found the human version of the gene in 2001. It also moves the search for the gene from the X chromosome to the 22 other types of chromosomes found in human cells, she adds.

In mammals, one of the two X chromosomes inherited by all females is turned off during development to prevent a dangerous double dose of proteins. A gene called Xist unquestionably turns off X chromosomes in mice, humans and other mammals. Because every cell needs one active X chromosome, Xist must be suppressed on one X in both females and males (which have an X and a Y chromosome). Which gene (or genes) does this is still in question, says Migeon.


In mice, researchers elsewhere pointed to the Tsix gene, because it suppressed Xist and was itself expressed only on the active X. However, studying cells from various human developmental stages, Migeon and her team discovered that human Tsix is expressed only on the inactive X chromosome, right alongside Xist. The two continue to be expressed together until after birth, when for reasons unknown Tsix gradually disappears.

"The difference is striking," says Migeon, also a professor of pediatrics. "In mice, researchers have suggested that Tsix was the gene in mammals that suppresses Xist and allows an X chromosome to remain active, but we’ve shown clearly that it does not do this in humans."

Migeon suggests instead that the mouse Tsix is involved in imprinting, a way cells determine which of two gene copies to use to make proteins that depends only on which parent the copy came from. In mice, X-inactivation in the placenta is imprinted -- the X from the mother is always "on." In other embryonic tissues, however, inactivation occurs randomly -- the X from either the mother or father could be on. In humans, X-inactivation is random for all tissues, including the placenta.

"Human and mouse Tsix are very different from one another," says Migeon. "Sequence differences and missing regions in human Tsix are a window on what’s happening in the mouse and help explain why the gene doesn’t have the same function in humans."

Much remains unknown about human Tsix, including what, if anything, it does in humans. However, Migeon will leave those mysteries for others to investigate, choosing instead to continue a 30-year quest to fully understand X-inactivation in human development.

"We expect to find a gene on one of the other chromosomes that turns off Xist in a random fashion," says Migeon. "It is difficult to envision how a gene on the X chromosome could, by itself, regulate the function of Xist on only one member of the X chromosome pair."

To track down Xist’s true suppressor, Migeon and her colleagues are studying human cells with "trisomies" -- cells that have 23 pairs of chromosomes plus a third copy of one chromosome. In these cells, if the Xist-suppressing gene is on the chromosome with three copies, X-inactivation would be abnormal, Migeon says.


The studies were funded by the National Institutes of Health. Authors on the study are Migeon, Catherine Lee, Ashis Chowdhury and Heather Carpenter, all of Johns Hopkins.

Joanna Downer | EurekAlert!
Further information:
http://www.journals.uchicago.edu/AJHG/journal/issues/v71n2/024004/024004.web.pdf
http://www.hopkinsmedicine.org

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>