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 The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

Quantum optical sensor for the first time tested in space – with a laser system from Berlin

23.01.2017 | Physics and Astronomy

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>