The structure of DNA is found to be actively involved in genome regulation
(Press-News.org) The two meters of -stretched- DNA contained in human cells are continuously twisting and untwisting to give access to genetic information: when a gene is expressed to generate a protein, the two strands of DNA are separated to give access to all the machinery necessary for this expression, resulting in an excessive accumulation of coiling that needs to be resolved later. The paper that has now been published by the team led by Felipe Cortés, head of the DNA Topology and Breaks Group at the Spanish National Cancer Research Centre (CNIO), in collaboration with Silvia Jimeno González, professor at the University of Seville and head of the mRNA Transcription and Processing Group at the Andalusian Centre for Molecular Biology and Regenerative Medicine (CABIMER), shows that this supercoiling characteristic of DNA's structure controls gene expression rather than being a mere collateral damage to be solved, as had been thought to date. The results are reported in the journal Cell Reports.
"These results are a first step towards understanding supercoiling as an important regulator of the genome and not only as a problem associated with the metabolism of DNA," says Cortés.
According to the paper's authors, this regulation occurs mainly on specific genes, namely those that are induced very quickly, hundreds of times in only a few minutes, such as the genes that respond to stress, cell proliferation signals, hormones or those involved in neuronal stimulation.
TOP2A, regulator of the expression of immediate response genes.
Topoisomerases are proteins that act on DNA, relaxing this topological stress by eliminating both an excess (positive supercoiling) and a defect (negative supercoiling) in the number of turns of the double helix compared to its normal relaxed structure.
The researchers demonstrated in this study that topoisomerase TOP2A eliminates negative supercoiling at gene promoters, thereby causing an increase in the number of turns of DNA strands in these regions. This hinders the opening of the double helix, preventing the RNA polymerase from advancing and leaving it ready to quickly trigger gene activation when required by the cell.
"Topoisomerases are considered gene activation facilitators, although here we demonstrate that topoisomerase TOP2A acts in the promoter regions of genes such as c-FOS [cell proliferation regulator] to keep them repressed, but creating a particular topological context that allows them to be activated quickly in order to provide an immediate response to stimuli," says Cortés.
The researchers also advance the possibility of other functions of DNA supercoiling, such as facilitating a three-dimensional conformation of the genome favouring interactions between regulatory elements for gene expression.
This new form of genomic regulation through supercoiling highlights its potential involvement in processes that are fundamental to cell function and that require profound changes in gene expression programmes, such as cell differentiation or reprogramming, as well as in tumour transformation and progression.
"The paper also opens up the possibility of using topoisomerase inhibitors to modulate these processes and cellular responses, and perhaps even as possible anti-tumour therapies," concludes Cortés.
The research was funded by the Ministry of Science and Innovation, the Carlos III Health Institute, the Government of Andalusia, the European Research Council and the Spanish Association Against Cancer.
ELSE PRESS RELEASES FROM THIS DATE:
Neonatal hypothermia -- which occurs when an infant's core body temperature falls below the normal range needed to maintain health -- contributes to approximately one million deaths each year, and countless cases of stunted growth, almost exclusively in low- and middle-income countries. To address this common but preventable condition, researchers from Boston Children's Hospital, engineers at Lawrence Berkeley National Laboratory, and colleagues in Rwanda developed the Dream Warmer, a low cost, reusable non-electric infant warmer to prevent and treat hypothermia. A new study from the team shows that infants who received treatment with the warmer had only an 11 percent rate of ...
A new experiment shows that the more energy consumed by a clock, the more accurate its timekeeping.
Clocks pervade every aspect of life, from the atomic clocks that underlie satellite navigation to the cellular clocks inside our bodies. All of them consume energy and release heat. A kitchen clock, for example, does this by using up its battery. Generally the most accurate clocks require the most energy, which hints at a fundamental connection between energy consumption and accuracy. This is what an international team of scientists from Lancaster, Oxford, and Vienna set out to test.
To do this, they built a particularly simple clock, consisting of a vibrating ultra-thin membrane, tens of nanometers ...
A research team from the Skoltech Center for Design, Manufacturing and Materials (CDMM) studied the effects of processing additives - aluminum hydroxide and zinc stearate - on the polymerization kinetics of thermosets used in pultrusion. The research was published in the Journal of Composite Materials.
Fiber-reinforced plastic (FRP) structural elements that have obvious advantages over conventional materials, such as steel, wood, and concrete, are widely used in civil, marine and road construction. FRP structures are manufactured using the pultrusion process, in which polymerization is achieved by continuously pulling ...
A new University of Iowa study challenges the idea that gray matter (the neurons that form the cerebral cortex) is more important than white matter (the myelin covered axons that physically connect neuronal regions) when it comes to cognitive health and function. The findings may help neurologists better predict the long-term effects of strokes and other forms of traumatic brain injury.
"The most unexpected aspect of our findings was that damage to gray matter hubs of the brain that are really interconnected with other regions didn't really tell us much about how poorly people would do on cognitive tests after brain damage. On the other hand, people with damage to the densest white matter connections did much worse on those tests," explains Justin Reber, PhD, ...
Training the artificial intelligence models that underpin web search engines, power smart assistants and enable driverless cars, consumes megawatts of energy and generates worrying carbon dioxide emissions. But new ways of training these models are proven to be greener.
Artificial intelligence models are used increasingly widely in today's world. Many carry out natural language processing tasks - such as language translation, predictive text and email spam filters. They are also used to empower smart assistants such as Siri and Alexa to 'talk' to us, and to operate driverless cars.
But to function ...
To observe the swift neuronal signals in a fish brain, scientists have started to use a technique called light-field microscopy, which makes it possible to image such fast biological processes in 3D. But the images are often lacking in quality, and it takes hours or days for massive amounts of data to be converted into 3D volumes and movies.
Now, EMBL scientists have combined artificial intelligence (AI) algorithms with two cutting-edge microscopy techniques - an advance that shortens the time for image processing from days to mere seconds, while ensuring that the resulting images are crisp and accurate. The findings are published in Nature Methods.
"Ultimately, we were able to take 'the best of both worlds' in this approach," says Nils Wagner, one of the paper's two lead ...
PHILADELPHIA-- A gene called GAS2 plays a key role in normal hearing, and its absence causes severe hearing loss, according to a study led by researchers in the Perelman School of Medicine at the University of Pennsylvania.
The researchers, whose findings are published online today in Developmental Cell, discovered that the protein encoded by GAS2 is crucial for maintaining the structural stiffness of support cells in the inner ear that normally help amplify incoming sound waves. They showed that inner ear support cells lacking functional GAS2 lose their amplifier abilities, causing severe hearing ...
Depressive symptoms are more common in teenage girls than in their male peers. However, boys' mental health appears to be affected more if they suffer from obesity. Irrespective of gender, bullying is a considerably greater risk factor than overweight for developing depressive symptoms. These conclusions are drawn by researchers at Uppsala University who monitored adolescents for six years in a questionnaire study, now published in the Journal of Public Health.
"The purpose of our study was to investigate the connection ...
Nearly four-fifths of 16- and 17-year-olds have encountered pornographic content on the Internet
Pornography is a multibillion-dollar business. Pornographic content is virtually ubiquitous on the Internet, and surveys suggest that 25% of all searches lead to explicit content. Given the size of the market, it's not surprising that young people are drawn to such sites, which are only a couple of clicks away.
Professor Neil Thurman of the Department of Media and Communication (IfKW) at Ludwig-Maximilians-Universitaet (LMU) in Munich, in collaboration with statistician Fabian Obster (Universität der Bundeswehr München), has carried out a study on the use of pornographic sites by young people. Based on a survey involving a sample ...
Great reed warblers normally migrate by night during its month-long migration from northern Europe to Sub-Saharan Africa. However, researchers have now discovered that during the few occasions when it continues to fly during daytime, it flies at extremely high altitudes (up to 6300 meters). One possible explanation for this unexpected and consistent behaviour could be that the birds want to avoid overheating. The study is published in Science.
Most of the many millions of songbirds that migrate every year between Europe and Africa fly by night and spend the daytime hours resting and eating. Some species, which normally only fly by night, occasionally fly for over 24 consecutive ...
LAST 30 PRESS RELEASES:
[Press-News.org] The structure of DNA is found to be actively involved in genome regulation