Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Aurora B answers an XIST-ential question

25.08.2009
Mitotic release of chromatin-binding RNA gives insight into X chromosome silencing

Early in development, mammalian female cells counteract their double dose of X chromosomes by coating one of them with a large RNA named XIST. The RNA binds to the same X chromosome from which it is transcribed and initiates a series of events leading to the chromosome's permanent silencing.

In the August 24, 2009 issue of the Journal of Cell Biology (www.jcb.org), Hall et al. exploit the fact that XIST temporarily dissociates from the X chromosome during mitosis and find that Aurora B kinase helps regulate the RNA's chromatin binding.

Although more than 10 years have passed since XIST was shown to paint the inactivated X (Xi) chromosome, little is known of how the 14-kb, noncoding transcript binds its target. "We know it doesn't just bind the DNA, but no specific binding proteins have been identified," says lead author Lisa Hall.

Biochemical approaches to finding protein partners may have been hampered by XIST's large size and tight association with the X chromosome, making it hard to extract the RNA complex and study it in vitro. So Hall, together with colleagues in Jeanne Lawrence's laboratory at the University of Massachusetts Medical School, took an in vivo approach—mimicking the events that cause XIST to drop off the Xi in early prophase.

Hall and colleagues found that treating cells with an inhibitor of protein phosphatase 1 (PP1) caused XIST to be released from the Xi in interphase cells. PP1 usually keeps the kinase Aurora B in check until the start of mitosis, so the team wondered whether XIST's premature release was driven by increased Aurora B activity. XIST was no longer released in interphase cells if PP1 and Aurora B were both inhibited. Moreover, inhibiting Aurora B with either drugs or a specific siRNA caused XIST to be retained on the Xi even in mitotic cells.

Lawrence says that the team was excited to identify Aurora B as a regulator of XIST. Their previous studies had suggested that a broader chromatin organizer might control XIST binding, particularly during cancer when the regulation of XIST and the Xi often goes awry. Aurora B fits the bill perfectly as it localizes to the chromosome arms at prophase, phosphorylates several chromatin proteins including histone H3, and is frequently activated in cancer cells.

It remains unclear exactly how Aurora B promotes XIST's loss from the Xi. "There are probably multiple places that XIST anchors to chromatin," says Lawrence. "In order to release it, you have to modify multiple points." Further studies on the mitotic loss of XIST should help identify these different anchor points and determine how they are modified to promote or block RNA binding.

XIST may, in fact, represent a broader class of noncoding RNAs that associate with and regulate heterochromatin. "We hope that manipulating binding in vivo provides a new way to study RNA–chromatin interactions that other labs will build on," says Lawrence. "It will be interesting to determine if these other RNAs mirror the behavior of XIST and are controlled by the same mechanism."

About the Journal of Cell Biology

Founded in 1955, the Journal of Cell Biology (JCB) is published by the Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license.

Hall, L.L., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200811143

Rita Sullivan | EurekAlert!
Further information:
http://www.jcb.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 >>>