Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Why developing nerve cells can take a wrong turn


Loss of ubiquitin-conjugating enzyme leads to impediment in growth of nerve cells / Link found between cellular machineries of protein degradation and regulation of the epigenetic landscape in human embryonic stem cells

A group of scientists from CECAD, the Cluster of Excellence ‘Cellular Stress Responses in Aging-Associated Diseases,’ have found a mechanism by which neurodevelopmental diseases concerning neurons can be explained:

The loss of a certain enzyme, UBE2K, impeded the differentiation of stem cells by silencing the expression of genes important for neuronal differentiation and, therefore, the development and generation of neurons.

More specifically, UBE2K regulates the levels and activation of histones, key proteins that pack and organize the DNA, regulating the expression of genes. Being part of the epigenetic landscape of the cell, the changes made to the histones are reversible and could provide a chance for future developments of treatments for neurodevelopmental diseases. The study is available in the current issue of Communications Biology.

Embryonic stem cells (ESCs) can replicate indefinitely while retaining their potential to differentiate into all other types of cells. Thus, nerve cells (neurons), muscle cells and all the other cells of the body are produced in a developing organism. Errors during this process can lead to congenital diseases. Degrading damaged proteins within the cell is an important factor in this process.

Thus, the scientists studied the interaction between the proteasome, the main protagonist in terminating proteins, and the epigenetic landscape. Epigenetic landscapes are the heritable changes to an organism which are not determined by DNA but through changes to the chromatin, which can organize and silence DNA into tighter packages.

Azra Fatima from CECAD studied the interactions of the histones in immortal human embryonic stem cells (hESCs) which have a unique chromatin architecture and especially low levels of a certain histone called H3 which has undergone a chemical addition in the form of three methylgroups (H3K9me3).

Histones are proteins which are part of the chromatin in cell nuclei. They build up spools around which the DNA winds, shortening it by a ratio of 1:10 millions. They are also responsible for regulating the gene expression by which genes produce proteins in the organism.

In addition, they play an important role in the process of cellular differentiation in which a cell, for example an embryonic stem cell, changes into another type of cell with a higher degree specialization.

They found that embryonic stem cells exhibit high expression of UBE2K (Ubiquitin-conjugating enzyme E2 K), a ubiquitin-conjugating enzyme. These enzymes are known for being important in the process of degradation of proteins.

The loss of the enzyme in embryonic stem cells caused an increase in the levels of H3K9 trimethyltransferase SETDB1, resulting in higher trimethylation of H3K9, leading in turn to a repression of neurogenic genes during the differentiation of the stem cells.

As a result, the loss of UBE2K impaired the ability of the stem cells to differentiate into neural progenitors a type of precursor cell that generate neurons and other cells of the nervous system.

Besides H3K9 trimethylation, the scientists found that UBE2K binds histone H3 to induce its polyubiquitination and degradation by the 26S proteasome. Notably, ubc-20, the worm orthologue of UBE2K, also regulates both histone H3 levels and H3K9 trimethylation in the germ cells of the model organism C. elegans.

‘Our results indicate that UBE2K crosses evolutionary boundaries to promote histone H3 degradation and reduce H3K9me3 repressive marks in immortal cells like human embryonic stem cells and germline cells”, says Fatima.
‘We found a link between the ubiquitin-proteasome system and epigenetic regulation in immortal stem cells,’ Fatima concluded.

‘It would be also interesting to see if UBE2K regulates the epigenetic state in other cell types like cancer cells.’ David Vilchez, the corresponding author of the manuscript, added: ‘We believe that our findings can have important implications to understand the development of the human brain.’

By precisely regulating the levels of UBE2K it would be possible to determine the cell type specific epigenetic landscapes. Different diseases like Huntington’s disease are associated with alterations in epigenetic marks. Since the epigenetic marks are reversible, it will be interesting to study if the epigenetic status of pluripotent stem cells from patients can be modulated by controlling the proteasome system and UBE2K.

In order to correct the disease phenotype, novel strategies could be designed to correct epigenetic alterations in early developmental stages and thus provide a potential treatment for diseases.

Media Contact:
Dr. Azra Fatima
Press and Communications Team:
Robert Hahn
+49 221 470 2396

Verantwortlich: Dr. Patrick Honecker MBA –

Gabriele Meseg-Rutzen | idw - Informationsdienst Wissenschaft
Further information:

More articles from Life Sciences:

nachricht Exploring Rapid Changes in the Arctic Ecosystem
07.07.2020 | Helmholtz-Zentrum Geesthacht - Zentrum für Material- und Küstenforschung

nachricht Gene duplication and disease: the downside of specialization
07.07.2020 | Universität Stuttgart

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Latest News

Nutrients in microalgae: an environmentally friendly alternative to fish

07.07.2020 | Health and Medicine

Mobile measuring instruments: Caught in flight

07.07.2020 | Power and Electrical Engineering

Exploring Rapid Changes in the Arctic Ecosystem

07.07.2020 | Life Sciences

Science & Research
Overview of more VideoLinks >>>