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:3/23/2016)... March 23, 2016 ... Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender Anbieter ... Unternehmen mit SpeechPro zusammenarbeitet, um erstmals dessen ... wird die Möglichkeit angeboten, im Rahmen mobiler ...
(Date:3/22/2016)... PROVO and SANDY, ... Screening Ontario (NSO), which operates the highest sample volume ... testing, and Tute Genomics and UNIConnect, leaders in clinical ... today announced the launch of a project to establish ... testing panel. NSO has been contracted ...
(Date:3/18/2016)... LONDON , March 18, 2016 ... Established Suppliers of Biometrics, ICT, Manned & Unmanned Vehicles, Physical ... & security companies in the border security market and ... and Europe has led ... your companies improved success. --> defence & ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... -- Sequenom, Inc. (NASDAQ: SQNM ), a life ... development of innovative products and services, announced today that ... denied its petition to review decisions by ... Patent No. 6,258,540 (",540 Patent") are not patent eligible ... Court,s Mayo Collaborative Services v. Prometheus Laboratories decision.  In ...
(Date:6/27/2016)... Diego, CA (PRWEB) , ... June 27, 2016 , ... ... solutions for clinical trials, announced today the Clinical Reach Virtual Patient Encounter ... their care circle with the physician and clinical trial team. , Using the CONSULT ...
(Date:6/27/2016)... ... June 27, 2016 , ... Rolf K. ... the faculty of the University of North Carolina Kenan-Flagler Business School ... entrepreneurship at UNC Kenan-Flagler, with a focus on the school’s international efforts, leading ...
(Date:6/27/2016)... Ginkgo Bioworks , a leading organism design company ... as one of the World Economic Forum,s Technology ... companies. Ginkgo Bioworks is engineering biology to manufacture ... the nutrition, health and consumer goods sectors. The ... Fortune 500 companies to design microbes for their ...
Breaking Biology Technology: