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 Novel 'repair system' discovered in algae may yield new tools for biotechnology
29.07.2016 | Boyce Thompson Institute

nachricht Molecular troublemakers instead of antibiotics?
29.07.2016 | Christian-Albrechts-Universität zu Kiel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-assembling nano inks form conductive and transparent grids during imprint

Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.

To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...

Im Focus: The Glowing Brain

A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology

On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...

Im Focus: Newly discovered material property may lead to high temp superconductivity

Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.

While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2016: 7th Conference on the Art, Technology and Theory of Digital Games

29.07.2016 | Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

 
Latest News

Vortex laser offers hope for Moore's Law

29.07.2016 | Power and Electrical Engineering

Novel 'repair system' discovered in algae may yield new tools for biotechnology

29.07.2016 | Life Sciences

Clash of Realities 2016: 7th Conference on the Art, Technology and Theory of Digital Games

29.07.2016 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>