Atlas of mouse and man

The functions of the different tissues in mammals are determined by which genes are expressed in them. Gene expression is controlled by transcription factors, which can attach to gene promoters either to induce them or to repress them. Transcription factors rarely work independently. Rather, they form combinations that affect the transcription of DNA.

An international team of researchers, including six from the King Abdullah University for Science and Technology (KAUST) in Saudi Arabia, managed to map 1,988 human and 1,727 mouse transcription factors. They produced an atlas of >1,600 combinations in humans and mice. This resource, which is available online, can help to study how the different combinations affect DNA-transcription regulation, giving rise to the specificity of tissues.

The analysis performed by the team suggests that tissue identity is determined not by having specific transcription factors, but rather by the formation of combinations of these substances that are unique to the tissue. In fact, the majority of transcription factors were found to be expressed widely in different tissues. When two transcription factors interact, they gain a new function, leading to specific gene expression in the cell. This gives rise to different tissues with different functions. In the model that the authors suggest, the combinations are made up of two distinct types of transcription factor: one that is tissue specific and another that is broadly expressed across different tissues.

The researchers plan to use the data in future work to study how these different combinations relate to an individual's health and well-being. They also suggest that the data could further be used to study network conservation and divergence over mammalian evolution, by studying the maps formed for humans and mice.

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