Rice University-based models simulate how nucleosomes facilitate gene exposure
The protein complex that holds strands of DNA in compact spools partially disassembles itself to help genes reveal themselves to specialized proteins and enzymes for activation, according to Rice University researchers and their colleagues.
Rice University scientists simulated a nucleosome coiled in DNA to discover the interactions that control its unwinding. The DNA double helix binds tightly to proteins (in red, blue, orange and green) that make up the histone core, which exerts control over the exposure (center and right) of genes for binding.
Credit: Wolynes Lab/Rice University
The team's detailed computer models support the idea that DNA unwrapping and core protein unfolding are coupled, and that DNA unwrapping can happen asymmetrically to expose specific genes.
The study of nucleosome disassembly by Rice theoretical biological physicist Peter Wolynes, former Rice postdoctoral researcher Bin Zhang, postdoctoral researcher Weihua Zheng and University of Maryland theoretical chemist Garegin Papoian appears in the Journal of the American Chemical Society. The research is part of a drive by Rice's Center for Theoretical Biological Physics (CTBP) to understand the details of DNA's structure, dynamics and function.
The spools at the center of nucleosomes, the fundamental unit of DNA organization, are histone protein core complexes. Nucleosomes are buried deep within a cell's nucleus. About 147 DNA base pairs (from the more than 3 billion in the human genome) wrap around each histone core 1.7 times. The double helix moves on to spiral around the next core, and the next, with linker sections of 20 to 90 base pairs in between.
The structure helps squeeze a 6-foot-long strand of DNA in each cell into as compact a form as possible while facilitating the controlled exposure of genes along the strand for protein expression.
The spools consist of two pairs of heterodimers, macromolecules that join to form the core. The core is stable until genes along the DNA are called upon by transcription factors or RNA polymerases; the researchers' goal was to simulate what happens as the DNA unwinds from the core, making itself available to bind to outside proteins or make contact with other genes along the strand.
The researchers used their energy landscape models to simulate the nucleosome disassembly mechanism based on the energetic properties of its constituent DNA and proteins. The landscape maps the energies of all the possible forms a protein can take as it folds and functions. Conceptual insights from energy landscape theory have been implemented in an open-source biomolecular modeling framework called AWSEM Molecular Dynamics, which was jointly developed by the Papoian and Wolynes groups.
Wolynes said most studies elsewhere treated the histone core as if it were rigid and irreversibly disassociated when DNA unwrapped. But more recent experimental studies that involved gently pulling strands of DNA or used fluorescent resonance energy transfer, which measures energy moving between two molecules, showed the protein core is flexible and does not completely disassemble during unwrapping.
In their simulations, the researchers found the core changed its shape as the DNA unwound. Without DNA, they found the histone core was completely unstable in physiological conditions.
Their simulations showed that histone tails - the terminal regions of the core proteins - play a crucial role in nucleosome stability. The tails are highly charged and bind tightly with DNA, keeping its genomic content from being exposed until necessary. Their models predicted a faster unwrapping for tail-less nucleosomes, as seen in experiments.
The nucleosome study is part of a larger effort both by Papoian at Maryland and by Wolynes with his colleagues at CTBP to understand the mechanics of DNA, from how it functions to how it reproduces during mitosis. Wolynes said the new study and another new one by his lab on DNA during mitosis represent the opposite ends of the size scale.
"We can understand things at each end of the scale, but there's a no-man's land in between," he said. "We'll have to see whether the phenomena in the present-day no-man's land can be understood. I don't believe in magic; I believe they eventually will."
Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, a professor of chemistry, of biochemistry and cell biology, of physics and astronomy and of materials science and nanoengineering at Rice and a senior investigator of the National Science Foundation (NSF)-funded CTBP. Papoian is the Monroe Martin Professor and chemical physics director at the University of Maryland. Zhang will join the Massachusetts Institute of Technology as an assistant professor in July.
The research was supported by the NSF, the CTBP and the National Institute of General Medical Sciences.
The researchers used the NSF-supported DAVinCI supercomputer administered by Rice's Ken Kennedy Institute for Information Technology.
Read the abstract at http://pubs.
This news release can be found online at http://news.
Follow Rice News and Media Relations via Twitter @RiceUNews.
Wolynes Research Lab: http://wolynes.
Papoian Lab: http://papoian.
Associative memory, Water mediated, Structure and Energy Model (AWSEM) protein simulation: http://awsem-md.
Center for Theoretical Biological Physics: https:/
Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for best quality of life and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.
David Ruth | EurekAlert!
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy