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.
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.
U Tokyo Research article
Euan McKay | ResearchSEA
Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University
Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University
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...
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...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
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...
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...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
27.03.2017 | Earth Sciences
27.03.2017 | Life Sciences
27.03.2017 | Life Sciences