Featured Research

from universities, journals, and other organizations

Mitotic Release Of Chromatin-binding RNA Gives Insight Into X Chromosome Silencing

Date:
September 6, 2009
Source:
Rockefeller University Press
Summary:
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. Researchers recently exploited 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 XIST initiates the silencing of the chromosome, the RNA (green) is temporarily released during mitosis (left). By manipulating XIST binding in vivo, Hall et al. discover that Aurora B kinase regulates the RNA’s association with chromatin: XIST is retained on the X chromosome in mitotic cells lacking Aurora B (right).
Credit: Hall, L.L., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200811143

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, 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."


Story Source:

The above story is based on materials provided by Rockefeller University Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lisa L. Hall, Meg Byron, Gayle Pageau, and Jeanne B. Lawrence. AURKB-mediated effects on chromatin regulate binding versus release of XIST RNA to the inactive chromosome. Journal of Cell Biology, 2009; DOI: 10.1083/jcb.200811143

Cite This Page:

Rockefeller University Press. "Mitotic Release Of Chromatin-binding RNA Gives Insight Into X Chromosome Silencing." ScienceDaily. ScienceDaily, 6 September 2009. <www.sciencedaily.com/releases/2009/08/090824115754.htm>.
Rockefeller University Press. (2009, September 6). Mitotic Release Of Chromatin-binding RNA Gives Insight Into X Chromosome Silencing. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2009/08/090824115754.htm
Rockefeller University Press. "Mitotic Release Of Chromatin-binding RNA Gives Insight Into X Chromosome Silencing." ScienceDaily. www.sciencedaily.com/releases/2009/08/090824115754.htm (accessed July 28, 2014).

Share This




More Plants & Animals News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Newsy (July 28, 2014) The asteroid that killed the dinosaurs struck at the worst time for them. A new study says that if it hit earlier or later, they might've survived. Video provided by Newsy
Powered by NewsLook.com
Raw: Sea Turtle Hatchlings Emerge from Nest

Raw: Sea Turtle Hatchlings Emerge from Nest

AP (July 27, 2014) A live-streaming webcam catches loggerhead sea turtle hatchlings emerging from a nest in the Florida Keys. (July 27) Video provided by AP
Powered by NewsLook.com
Russia Saves Gecko Sex Satellite, Media Has Some Fun With It

Russia Saves Gecko Sex Satellite, Media Has Some Fun With It

Newsy (July 27, 2014) The satellite is back under ground control after a tense few days, but with a gecko sex experiment on board, the media just couldn't help themselves. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins