A study that could point the way towards the development of cures for Parkinson's, Alzheimer's, liver disease and diabetes has been published by a team that includes three researchers from King Abdullah University of Science and Technology (KAUST). The group of systems biologists and engineers employed innovative techniques to study transcription factors (TFs), proteins that play a crucial role in tissue development by orchestrating the transcriptional networks underlining this tightly controlled process. Combinatorial interaction among TFs results in the differentiation of different types of tissue – for example combinations lead to the differentiation of muscle tissue or brain tissue.

The genetic template for each tissue type is contained in DNA, and the TFs control the transfer – or transcription – of this information by binding with specific sequences of DNA.

The process by which this information is used to create different types of cell is known as tissue-specific gene expression, and the way that TFs combine to control this process is known as combinatorial regulation.

The research team has compiled the first catalogue of TF combinations in mice and men, identifying networks containing roughly 5,000 interactions between TFs. The two types of mammal were used to double-check the findings and eliminate misleading results known as false positives. And the team discovered that roughly half of the interactions between TFs that they observed were common to both mice and men.

Previous studies examined the behavior of individual TFs in isolation but the new report is the first to describe how they act when they combine. "The data highlight the importance of TF combinations for determining cell fate," says the report. "The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution."

The paper, An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man, has been published as the cover article in the top-rated journal Cell. The lead author is Dr Timothy Ravasi, Principal Investigator at the Red Sea Laboratory of Integrative Systems Biology and Associate Professor of Bioengineering, who worked with post-doctoral fellow Carlo Vittorio Cannistraci and Vladimir Bajic, Director of the Computational Bioscience Research Center and Professor, Applied Mathematics and Computational Science.