Mapping the power of networking


   Research Highlights


An atlas of TF–TF interaction networks in humans and mice may offer powerful new insights into the principles of gene regulation and reveal new strategies for treating disease.

However, the TF–gene relationship is seldom simple. “In many cases, TFs work as complexes in which two or more proteins physically interact,” explains Dr. Timothy Ravasi, Professor of Bioengineering at KAUST. “Depending on the combination, expression of different sets of genes is regulated; thus, these protein–protein interactions are essential information for analysis of transcriptional network regulation.”

Ravasi and his group determined where each TF is produced in an effort to classify individual factors as tissue-localized ‘specifiers’ or broadly expressed ‘facilitators’. Further analysis enabled them to identify clusters of interactions associated with different subsets of tissues, revealing a fraction of TF–TF associations that help coordinate the development of embryonic tissue into the diverse range of cell types seen in mature organisms. “We identified a small protein–protein interaction sub-network consisting of only 15 TFs, which plays a crucial role in the regulation of cell fate,” says Ravasi. Strikingly, this network contained mostly promiscuously expressed ‘facilitators’, suggesting that the localization of multi-factor interactions is as important as the restricted expression of individual factors in governing tissue-specific gene expression.