Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transcriptional mechanisms governing cartilage formation

08.07.2015

Genome-wide identification of Sox9 regulatory system

Researchers at the University of Tokyo have identified modes of Sox9 action during cartilage formation by analyzing big data on Sox9 location, chromatin state, and gene expression over the whole mouse genome.


Model for two distinct modes of Sox9 action in cartilage formation proposed in the present study. In Class I engagement, Sox9 binds to the genome indirectly via the basal transcriptional complex, regulating transcription of genes for basal cell activities. In Class II engagement, Sox9 binds to multiple active enhancer elements through sub-optimal, low-affinity Sox dimeric motifs (DNA sequences), resulting in a high level of transcription of cartilage-related genes. © 2015 Shinsuke Ohba.

This finding will contribute to the understanding of cartilage diseases caused by genomic mutation and genome-based drug discovery for disease therapies.

Cartilage generated in embryos not only regulates skeletal growth until puberty, but also plays a key role in our locomotion as articular cartilage in our joints. Cartilage formation (chondrogenesis) requires the normal function of Sox9, a protein that regulates the expression of chondrogenesis-related genes.

Mutation around the region of the human SOX9 gene, which encodes the Sox9 protein, causes campomelic dysplasia, a congenital disease that is accompanied by skeletal abnormalities and other conditions.

Although the mechanisms underlying Sox9-mediated transcriptional regulation during chondrogenesis have been intensively investigated at a certain genomic region, its genome-wide regulation remained unclear.

Project Associate Professor Shinsuke Ohba at the Department of Bioengineering, the University of Tokyo Graduate School of Engineering, identified two genome-wide modes (Class I and Class II engagement) of Sox9 action in transcription during chondrogenesis.

In Class I engagement, Sox9 binds indirectly to the DNA and regulates the transcription of genes involved in basal cell activities. In Class II engagement, it binds directly to the DNA in multiple locations and activates transcription of cartilage-related genes.

“This finding will contribute to the understanding of cartilage-related degenerative diseases and congenital abnormalities that are caused by genomic mutation and genome-based drug discovery for treatment of diseases and cartilage regeneration,” says Ohba.

This work was published in the online version of Cell Reports (Cell Press) on July 2, 2015. This research was carried out in collaboration with Professor Andrew P. McMahon at the University of Southern California.

Paper

Shinsuke Ohba, Xinjun He, Hironori Hojo, Andrew P. McMahon, "Distinct transcriptional programs underlie Sox9 regulation of the mammalian chondrocyte", Cell Reports Online Edition: 2015/7/3 (Japan time), doi: 10.1016/j.celrep.2015.06.013.


Associated links
U Tokyo Research article

Euan McKay | ResearchSEA
Further information:
http://www.researchsea.com

Further reports about: Cartilage Cell DNA Tokyo abnormalities action diseases drug discovery genes genomic identified mechanisms skeletal transcription

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown 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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>