Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transcription factors: function follows form

17.10.2013
Spatial structure determines transcription factor activity

Clay can be used in various forms for a range of objects such as cups, plates or bricks. Similarly, proteins can transform their structure and thus adapt their function and activity.


DNA-induced structural changes (parts that change are colored red) in the DNA binding domain of the glucocorticoid receptor (left) and the structural changes (red) that occur when an extra amino acid is inserted in the DNA binding domain of the glucocorticoid receptor as a consequence of alternative splicing (right).

© MPI f. Molecular Genetics/Meijsing

Researchers at the Max Planck Institute for Molecular Genetics in Berlin have analysed proteins for such modifications that control gene activity, so-called transcription factors. The researchers thereby discovered that DNA changes the form and the activity of the glucocorticoid receptor, and also ascertained how various domains in the molecule communicate with one another.

Furthermore, the way in which the protein domains are connected also changes as a result of the integration of individual amino acids in the protein chain. Different genes are therefore transcribed to varying degrees.

Transcription factors are responsible for transcribing the correct genes and therefore for producing the right quantity of proteins. They bind to specific sections of DNA near genes, such as promoters for example. However, the transcription factors do not function simply as an on/off switch but rather like a volume control, which allows gene expression to be precisely controlled.

The glucocorticoid receptor is a transcription factor, which, for example, is activated by the hormone cortisol during fasting, resulting in glucose production in the liver. Because of its anti-inflammatory effect, it also plays an important role in the treatment of illnesses caused by an overactive immune system, such as allergies, autoimmune diseases and asthma. Various signals determine its activity, two of which are: firstly, the DNA to which the glucocorticoid receptor binds in order to regulate the gene. The second signal is the integration of additional amino acids in the protein.

The Berlin-based Max Planck researchers have studied how these two signals have an effect, which genes are regulated by the glucocorticoid receptor and how they affect the strength of the regulation. “Our findings show that DNA is not simply a passive strip of Velcro which can be bound by proteins. Instead, DNA changes the shape of the proteins and thereby the communication between various protein domains,” explains Sebastiaan H. Meijsing from the Max Planck Institute for Molecular Genetics. In this way, the glucocorticoid receptor can adapt its activity to individual genes.

Furthermore, different variants of the glucocorticoid receptor exist. They occur when the original RNA chain, produced when the glucocorticoid receptor gene is transcribed, is subsequently modified again. During this process, known as alternative splicing, additional modules can be added to the amino acid chain in the protein. The modification changes the way in which different sections of the glucocorticoid receptor are connected to one another. As a result, different genes can be transcribed to varying degrees. “Transcription factors are like chameleons in the way they can change their appearance. It allows them to respond to different signals and regulate genes with particular precision,” says Meijsing.

Contact

Dr. Sebastian Meijsing
Max Planck Institute for Molecular Genetics, Berlin
Phone: +49 30 8413-1176
Email: meijsing@­molgen.mpg.de
Dr. Patricia Marquardt
Max Planck Institute for Molecular Genetics, Berlin
Phone: +49 30 8413-1716
Fax: +49 30 8413-1671
Email: patricia.marquardt@­molgen.mpg.de
Original publication
Morgane Thomas-Chollier, Lisa C. Watson, Samantha B. Cooper, Miles A. Pufall, Jennifer S. Liu, Katja Borzym, Martin Vingron, Keith R. Yamamoto, Sebastiaan H. Meijsing
A naturally occuring insertion of a single amino acid rewires trancriptional regulation by glucocorticoid receptor isoforms

PNAS, 14 October 2013

Dr. Sebastian Meijsing | Max-Planck-Institute
Further information:
http://www.mpg.de/7573582/transcriptions-factor_glucocorticoid-receptor?filter_order=L&research_topic=

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>