Navigation Links
Watching the cogwheels of the biological clock in living cells
Date:10/26/2012

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.


'/>"/>
Contact: Ueli Schibler
ueli.schibler@unige.ch
41-223-796-175
Universit de Genve
Source:Eurekalert  

Related biology news :

1. Self-forming biological scaffolding
2. Merging the biological and the electronic
3. Boston subway system to be used to test new sensors for biological agents
4. Making sense out of the biological matrix of bipolar disorder
5. Understanding the biological and ecological implications of safe nanotechnology
6. Iowa State, Ames Lab researchers invent new tool to study single biological molecules
7. Mathematicians find solution to biological building block puzzle
8. Allergies? Your sneeze is a biological response to the noses blue screen of death
9. Johns Hopkins researchers link 2 biological risk factors for schizophrenia
10. Golden West Biologicals, Inc. Exhibiting at AACC Clinical Lab Expo 2012
11. Biological and Pharmaceutical Complex Fluids Conference
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Watching the cogwheels of the biological clock in living cells
(Date:3/16/2017)... , March 16, 2017 CeBIT 2017 - Against identity fraud with ... Reading ... Used combined in one project, multi-biometric solutions provide a crucial ... Used combined in ... ...
(Date:3/7/2017)...   HireVue , the leading provider of video ... best talent, faster, today announced the additions of ... Diana Kucer as Chief Marketing Officer (CMO). ... poised to drive continued growth in the company,s new ... record bookings in 2017. "Companies worldwide turn ...
(Date:3/2/2017)... Australian stem cell and regenerative medicine company, ... an agreement with the Monash Lung Biology Network, a ... and Department of Pharmacology at Monash University, ... to support the use of Cymerus™ mesenchymal stem cells ... Asthma is a chronic, long term lung condition recognised ...
Breaking Biology News(10 mins):
(Date:3/20/2017)... (PRWEB) , ... March 20, ... ... substances that interfere with the ability of endogenous hormones to regulate homeostasis ... ligand binding activity (antagonists), EDCs produce adverse reproductive, neurological, proliferative, and immunological ...
(Date:3/20/2017)... ... March 20, 2017 , ... Existing methods using LC-MS/MS suffer ... to reduce the impact on instrumentation. ICP-MS is a robust and specific analytical ... , This presentation will discuss the pros and cons of using LC-ICP-MS for ...
(Date:3/20/2017)... ... March 20, 2017 , ... Park Systems, a leader in Atomic Force Microscopy ... 24, 2017 from 5-7pm at their Santa Clara facility that will include craft beer ... Researcher, Dr. Tae-Gon Kim. , Dr. Tae-Gon Kim, Senior researcher at imec Belgium and ...
(Date:3/20/2017)... , March 20, 2017  Attorney Advertising -- Bronstein, Gewirtz ... purchasers of the BioAmber Inc. ("BioAmber" or the "Company") (NYSE: ... information and assist the investigation by visiting the firm,s site: ... BioAmber and certain of its officers and/or directors have violated ... 1934. ...
Breaking Biology Technology: