Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Global crosstalk limits gene regulation

15.08.2016

Molecular recognition is fundamental to transcriptional regulation, the primary mechanism by which cells control gene expression.

The specificity of this regulation originates in the binding interactions between special regulatory proteins, called transcription factors (TFs), and short regulatory sequences on the DNA, called binding sites.


(a) A TF preferentially binds to its cognate binding site, but can also bind noncognate sites, potentially causing crosstalk--an erroneous activation or repression of a gene. (b) In a global setting where many TFs regulate many genes, the number of possible noncognate interactions grows quickly with the number of TFs; additionally, it may become difficult to keep TF recognition sequences sufficiently distinct from each other. (c) Cells respond to changing environments by attempting to activate subsets of their genes. In this example, the total number of genes is M = 4, and different environments (here, 6 in total) call for activation of differ- ent subsets with Q = 2 genes. To control the expression in every environment, TFs for Q required genes are present, while the TFs for the remaining M ? Q genes are absent. Because of crosstalk, TFs can bind noncognate sites, generating a pattern of gene expression that can differ from the one required.

Credit: IST Austria, 2016

Although each type of TF preferentially binds certain regulatory DNA sequences, evidence shows that this binding specificity is limited, and that TFs bind other noncognate targets, too.

If these sites happen to be regulatory elements of other genes, noncognate binding not only depletes TF molecules, but could also actively interfere with gene regulation. This suggests that the crosstalk problem is global.

In "Intrinsic limits to gene regulation by global crosstalk", a research paper published on August 4 in Nature Communications, ISTFellow Tamar Friedlander, PhD student Roshan Prizak, and Professors Calin Guet, Nick Barton and Gasper Tkacik construct a biophysical model for crosstalk in transcriptional regulation that accounts for all cross-interactions between regulators and their binding sites.

They identify the parameters that have a major influence on crosstalk severity. While some of these parameters are difficult to estimate, they show that there exists a lower bound to crosstalk with respect to these parameters. This implies the existence of a "crosstalk floor," which cannot be overcome even if TF concentrations were optimally adjusted by the cell and compensated for sequestration at noncognate sites.

Although most of the biophysical constraints have been understood at the level of individual genetic regulatory elements, the researchers find that crosstalk is special: while it originates locally due to biophysical limits to molecular recognition, its cumulative effect only emerges globally.

At the level of a single genetic regulatory element, crosstalk can always be avoided by increasing the concentration of cognate TFs or introducing multiple binding sites in the promoter. It is only when these same cognate TFs act as noncognate TFs for other genes, or that new binding sites in the promoter drastically increase the number of noncognate binding configurations, that crosstalk constraints become clear.

Media Contact

Stefan Bernhardt
stefan.bernhardt@ist.ac.at
43-224-39000

 @Istaustria

http://Www.ist.ac.at 

Stefan Bernhardt | EurekAlert!

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>