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 A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>