Navigation Links
Throwing a loop to silence gene expression
Date:9/2/2014

All human cells contain essentially the same DNA sequence their genetic information. How is it possible that shapes and functions of cells in the different parts of the body are so different? While every cell's DNA contains the same construction master plan, an additional regulatory layer exists that determines which of the many possible DNA programs are active. This mechanism involves modifications of genome-bound histone proteins or the DNA itself with small chemical groups (e.g. methylation). It acts on top of the genetic information and is thus called 'epi'-genetic from the corresponding Greek word that means 'above' or 'attached to'.

"Epigenetics has fundamentally changed our view on how the genetic information is used", says Dr. Karsten Rippe from the German Cancer Research Center, who is studying this process with his team. "Epigenetic modifications can be rapidly set or removed to reversibly change cell function. At the same time, epigenetic patterns can be stably inherited through cell division and possibly also to the next generation."

It turns out that deciphering the cell's 'epigenetic code' is a challenging task: Hundreds of proteins in the cell are linked in large networks to 'write', 'erase' or 'read' about 140 different chemical modifications of histone proteins and DNA that have been identified so far. Understanding how epigenetic regulation operates for a specific part of the genome thus requires an integrative approach that considers the connections between different factors. Accordingly, the researchers, together with their colleagues from the DKFZ and the LMU Munich, conducted a comprehensive analysis of a prototypic epigenetic network. They studied how certain DNA sequences were silenced by histone and DNA methylation that would make the genome instable if active and would thus favor cancer development.

Based on maps of epigenetic signals and interactions of proteins with the genome, they developed a mathematical model for epigenetic silencing. "The silencing mechanism we found works much like throwing a loop with a lasso to catch something", says Katharina Mller-Ott, the first author of the study: "Several factors bind the silencing enzyme stably to certain sites in the genome. Because the DNA randomly moves around and forms transient loops, the enzyme hits other regions in the genome nearby, which then become modified and are switched off."

By virtue of their quantitative description of this process, the researchers were able to predict how the silencing network would react in response to perturbations like changes of the abundance of proteins or the activity of the enzymes involved. The scientists in the groups of Karsten Rippe and Thomas Hfer at the DKFZ are now continuing to further develop and apply their model to deregulated epigenetic signaling in leukemia. By evaluating genome-wide maps of epigenetic signals with mathematical models they are identifying tumor-specific changes in cell samples from patients with blood cancer. Furthermore, they are dissecting how epigenetic signals can be used to predict therapy response and how drugs affect the epigenetic program.


'/>"/>

Contact: Dr. Sibylle Kohlstädt
s.kohlstaedt@dkfz.de
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
Source:Eurekalert

Related biology news :

1. Novel RNAi therapy silences mutated Huntingtons disease gene and reduces symptoms
2. IU biologists offer clearer picture of how protein machine systems tweak gene expression
3. A new application allows online statistical analysis of gene-expression data
4. Measuring progesterone receptor expression to improve hormone-receptor-positive cancer management
5. Fish show autism-like gene expression in water with psychoactive pharmaceuticals
6. Controlling gene expression with hydrogen peroxide switches
7. Molecular economics: New computer models calculate systems-wide costs of gene expression
8. Controlling gene expression: How chromatin remodelers block a histone pass
9. Study finds how BPA affects gene expression, anxiety; Soy mitigates effects
10. Nutrient in eggs and meat may influence gene expression from infancy to adulthood
11. Whitehead scientists identify major flaw in standard approach to global gene expression analysis
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/20/2017)... -- Delta (NYSE: DAL ) customers now can use fingerprints ... Washington National Airport (DCA). ... Delta launches biometrics to board aircraft at Reagan Washington National ... Delta,s biometric boarding pass experience that launched ... into the boarding process to allow eligible Delta SkyMiles Members who are ...
(Date:6/23/2017)... ITHACA, N.Y. , June 23, 2017 ... a leader in dairy research, today announced a new ... help reduce the chances that the global milk supply ... this dairy project, Cornell University has become the newest ... Food Supply Chain, a food safety initiative that includes ...
(Date:5/23/2017)... May 23, 2017  Hunova, the first robotic gym for the rehabilitation ... officially launched in Genoa, Italy . The first 30 ... and the USA . The technology was developed and ... by the IIT spin-off Movendo Technology thanks to a 10 million euro ... Release, please click: ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... ... Disappearing forests and increased emissions are the main causes of the evolving air ... living in larger cities are affected by air pollution related diseases. , That is ... globally - decided to take action. , “I knew I had to take action ...
(Date:10/10/2017)... CALIF. (PRWEB) , ... October 10, 2017 , ... San ... part of its corporate rebranding initiative announced today. The bold new look is ... reach, as the company moves into a significant growth period. , It will also ...
(Date:10/10/2017)... ... October 10, 2017 , ... Dr. Bob Harman, founder and ... San Diego Rotary Club. The event entitled “Stem Cells and Their ... 300+ attendees. Dr. Harman, DVM, MPVM was joined by two human doctors: Peter ...
(Date:10/10/2017)... SANTA BARBARA, CALIFORNIA (PRWEB) , ... October 10, ... ... risk management, technological innovation and business process optimization firm for the life sciences ... the BoxWorks conference in San Francisco. , The presentation, “Automating GxP ...
Breaking Biology Technology: