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 What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>