| Summary: | <p>Abstract</p> <p>Background</p> <p>Many cellular programs are regulated through the integration of specific transcriptional signals originated from external stimuli, being cooperation between transcription factors a key feature in this process. In this work, we studied how transcriptional cooperativity in yeast is aimed at integrating different regulatory inputs rather than controlling particular cellular functions from a organizational, evolutionary and functional point of view.</p> <p>Findings</p> <p>Our results showed that cooperative transcription factor pairs co-evolve and are essential for the life of the cell. When organized into a layered regulatory network, we observed that cooperative transcription factors were preferentially placed in the middle layers, which highlights a role in regulatory signal integration. We also observed significant co-activity and co-evolution between members of the same cooperative pairs, but a lack of common co-expression profile.</p> <p>Conclusions</p> <p>Our results suggest that transcriptional cooperativity has a specific role within the regulatory control scheme of the cell, focused in the amplification and integration of cellular signals rather than control of particular cellular functions. This information can be used for better characterization of regulatory interactions between transcription factors, aimed at determining the spatial and temporal control of gene expression.</p>
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