Featured Research

from universities, journals, and other organizations

Watching the cogwheels of the biological clock in living cells

Date:
October 26, 2012
Source:
Université de Genève
Summary:
Most physiological functions in mammals are controlled by a daily internal time-keeping system, termed the circadian clock. The transcription of many genes producing detoxifying enzymes is regulated by DBP, a protein that is itself expressed in a highly rhythmic fashion. Scientists have now deciphered the molecular basis of how the circadian clock controls the rhythmic production of DBP protein in individual living cells.

This is a picture of a living cell with fluorescent blue series of DBP gene copies...and stylized cogwheels.
Credit: Markus Stratmann & Nicolas Roggli / University of Geneva

Our master circadian clock resides in a small group of about 10'000 neurons in the brain, called the suprachiasmatic nucleus. However, similar clocks are ticking in nearly all cells of the body, as demonstrated by the group of Ueli Schibler, professor at the Department of Molecular Biology of the University of Geneva, Switzerland. The molecular mechanisms of circadian clocks can thus be studied outside of the animals, in cultured cells.

A system to study gene regulation live in single cells

"Given the important role of the DBP protein in the regulation of detoxifying enzymes, we were interested in studying the molecular mechanisms underlying the rhythmic transcription of the DBP gene," points out the biologist, who is member of the NCCR Frontiers in Genetics. To do so, his team devised an elegant method to watch directly under the microscope how the clock's molecular "cogwheels" govern the activity rhythms of this gene in individual living cells. To this end, the scientists engineered a cell line with a piece of a chromosome exclusively composed of repeated DBP gene copies. They showed that the daily transcription of DBP is due to the rhythmic association of an essential clock component, the transcription factor BMAL1. "This is the first time a transcription factor binding to a circadian gene could be visualized in real time in single cells" explains Markus Stratmann, first author of the article.

The clock transcription factor must be sacrificed

To their surprise, the scientists found that the clock protein BMAL1 is destroyed while stimulating the expression of the DBP gene. By applying a variety of sophisticated imaging and biochemical techniques, they showed that the BMAL1 molecules bound to the DBP gene are degraded by an intracellular protein destruction machine, termed the proteasome.

Curiously, the chopping of the triggering protein BMAL1 is absolutely required for the efficient activation of the DBP gene. In other words, BMAL1 must die while embracing that gene in order to do its job. "In a sense, these transcription factors have the same cruel fate as males of the carnivorous insect Mantis. Sadly, Mantis females decapitate and then start eating their partners before the act of love is even completed" says Markus Stratmann.

At the moment, the biologists can only speculate about the broader impact of their findings. "We do not yet understand why the destruction of the BMAL1 protein is mandatory for the optimal functioning of the DBP gene" remarks Ueli Schibler. In fact, BMAL1 molecules regulate the daily activity of many other genes without getting killed while doing their work. The researchers noticed, however, that genes whose activity is not associated with the destruction of BMAL1 are expressed many hours later than the DBP gene. Their work thus offers a plausible explanation to the enigma of how one and the same transcription factor, BMAL1, can impose dramatically different daily cycles of gene expression.


Story Source:

The above story is based on materials provided by Université de Genève. Note: Materials may be edited for content and length.


Journal Reference:

  1. Markus Stratmann, David Michael Suter, Nacho Molina, Felix Naef, Ueli Schibler. Circadian Dbp Transcription Relies on Highly Dynamic BMAL1-CLOCK Interaction with E Boxes and Requires the Proteasome. Molecular Cell, 2012; 48 (2): 277 DOI: 10.1016/j.molcel.2012.08.012

Cite This Page:

Université de Genève. "Watching the cogwheels of the biological clock in living cells." ScienceDaily. ScienceDaily, 26 October 2012. <www.sciencedaily.com/releases/2012/10/121026125007.htm>.
Université de Genève. (2012, October 26). Watching the cogwheels of the biological clock in living cells. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2012/10/121026125007.htm
Université de Genève. "Watching the cogwheels of the biological clock in living cells." ScienceDaily. www.sciencedaily.com/releases/2012/10/121026125007.htm (accessed September 17, 2014).

Share This



More Plants & Animals News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) — The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) — Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Raw: Scientists Examine Colossal Squid

Raw: Scientists Examine Colossal Squid

AP (Sep. 16, 2014) — Squid experts in New Zealand thawed and examined an unusual catch on Tuesday: a colossal squid. It was captured in Antarctica's remote Ross Sea in December last year and has been frozen for eight months. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) — Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
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