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 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>