Navigation Links
Aurora B answers an XIST-ential question
Date:8/24/2009

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 approachmimicking 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 RNAchromatin 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."


'/>"/>

Contact: Rita Sullivan
news@rupress.org
212-327-8603
Rockefeller University Press
Source:Eurekalert  

Related biology news :

1. New supercomputer to reel in answers to some of Earths problems
2. Grant to fund answers about St. Johns River
3. MIT: No easy answers in evolution of human language
4. Fungus genome yielding answers to protect grains, people and animals
5. Recent news reports of sweetener reformulations raise questions about motivations
6. Work of Field Museum scientist addresses question of chance in evolution
7. Ecologists question effects of climate change on infectious diseases
8. Mountain on Mars may answer big question
9. New models question old assumptions about how many molecules it takes to control cell division
10. Similar survival rates for Pacific salmon in Fraser, Columbia Rivers raises new questions
11. Study of polar dinosaur migration questions whether dinosaurs were truly the first great migrators
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Aurora B answers an XIST-ential question
(Date:3/30/2017)... HONG KONG , March 30, 2017 ... developed a system for three-dimensional (3D) fingerprint identification by adopting ground ... technology into a new realm of speed and accuracy for use ... applications at an affordable cost. ... ...
(Date:3/27/2017)... , March 27, 2017  Catholic Health ... and Management Systems Society (HIMSS) Analytics for achieving ... Adoption Model sm . In addition, CHS previously ... U.S. hospitals using an electronic medical record (EMR). ... its high level of EMR usage in an ...
(Date:3/23/2017)... Mar. 23, 2017 Research and Markets has ... Analysis & Trends - Industry Forecast to 2025" report to ... ... a CAGR of around 8.8% over the next decade to reach ... analyzes the market estimates and forecasts for all the given segments ...
Breaking Biology News(10 mins):
(Date:7/20/2017)... July 20, 2017   KCNQ2 Cure Alliance ... evaluations company, today announced that they have completed ... genetic mutation implicated in KCNQ2 epileptic encephalopathy. They ... a second case involving an additional KCNQ2 genetic ... Alliance and Pairnomix entered into a collaboration to ...
(Date:7/20/2017)... , ... July 20, 2017 , ... ... to make clinical trial sites and study participants truly unified. TrialKit, a native ... (FDA 21 CFR Part 11) research studies entirely on mobile devices. With TrialKit, ...
(Date:7/18/2017)... ... July 18, 2017 , ... Sourcing custom glass or quartz parts can be ... capabilities to properly execute your job can take many hours of emails, phone calls ... portal designed to showcase the company’s capabilities and core custom categories, and enables you ...
(Date:7/18/2017)... ... , ... G-CON today announced that it has received Notices ... Applications 14/858,857 and 13/669,785 both entitled Modular, Self-Contained, Mobile Clean Room. The U.S. ... of G-CON’s R&D investments and validate the G-CON platform as a novel way ...
Breaking Biology Technology: