Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein paves the way for correct stem cell differentiation

08.02.2013
A single embryonic stem cell can develop into more than 200 specialized cell types that make up our body.

This maturation process is called differentiation and is tightly regulated through strict control of gene activity. If the regulation is lost, specialized cells cannot develop correctly during development.


Fbxl10 allow PRC1 to bind to the DNA structure and enable PRC1 to silence the gene

In adulthood, the specialized cells may forget their identity and develop into cancer cells. Research from BRIC, University of Copenhagen, has identified a crucial role of the molecule Fbxl10 in differentiation of embryonic stem cells and suggests the molecule as a new potential target for cancer therapy.

“Our new results show that this molecule is required for the function of one of the most important molecular switches that constantly regulates the activity of our genes. If Fbxl10 is not present in embryonic stem cells, the cells cannot differentiate properly and this can lead to developmental defects”, says Professor Kristian Helin, who heads the research group behind the new findings.

Fbxl10 recruits and activates genetic switches

The Polycomb protein complexes PRC1 and PRC2 are some of the most important genetics switches, which control the fate of individual cells through negative regulation of gene activity. The mechanism by which PRCs are recruited to DNA has been elusive as they are not capable of binding DNA directly. The new results from the Helin research group provide a mechanism for how the PRCs are recruited to the genes that are to be silent.

“Our results show that Fbxl10 is essential for recruiting PRC1 to genes that are to be silenced in embryonic stem cells. Fbxl10 binds directly to DNA and to PRC1, and this way it serves to bring PRC1 to specific genes. When PRC1 is bound to DNA it can modify the DNA associated proteins, which lead to silencing of the gene to which it binds”, says postdoc Xudong Wu, who has led the experimental part of the investigation.

Fbxl10 is a potential target for cancer therapy

Timing of gene activity is not only crucial during development, but has to be maintained throughout the lifespan of any cell. Some genes are active at a certain times, but inactive at other times.. Here PRC1 comes into play. PRC1 is dynamically recruited to and dissociated from genes according to the needs of our organism. When cancer strikes, this tight regulation of gene activity is often lost and the cells are locked in a less differentiated stage. This loss of differentiation and the accumulation of other mutations allow the cancer cells to undergo indefinite self-renewal through endless cell divisions, an ability that normal differentiated cells are prohibited from through tight gene regulation.

“Given the emerging relationship between cancer and stem cells, our findings may implicate that an aberrant activity of Fbxl10 can disturb PRC function and promote a lack of differentiation in our cells. This makes it worth studying whether blocking the function of Fbxl10 could be a strategy for tumour therapy”, says Xudong Wu.

And that is exactly what the researchers want to try. In collaboration with the biotech company EpiTherapeutics, the researchers want to develop inhibitors to Fbxl10 as a potential novel therapy for cancer.

Original article: The results are published in the journal Molecular Cell on February 7, 2013: Wu et al.: Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation.

The work was supported by grants from the Danish National Research Foundation, the Danish Cancer Society, the Novo Nordisk Foundation, and the Excellence Program of the University of Copenhagen.

Contact
Professor Kristian Helin
Phone: +45 35325668

postdoc Xudong Wu
Phone: +45 35325818

Research Coordinator Katrine Sonne-Hansen
Phone: +45 35325648
Mobile: +45 25854742

Katrine Sonne-Hansen | EurekAlert!
Further information:
http://www.bric.ku.dk

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>