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.
Stefan Bernhardt | EurekAlert!
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences