Gene clustering drives co-regulation of disparate biological pathways in eukaryotes

The establishment of distinct transcriptional states in response to developmental or environmental cues is critical for survival. This involves the concordant or discordant transcriptional regulation of several distinct biological pathways, often involving thousands of genes. How these system-level changes to transcriptomes are coordinated is an understudied problem in eukaryotic biology. Here, using computational and experimental approaches in eukaryotes ranging from yeast to human, we report that this coordination is in part achieved by the genic proximity of the regulatory nodes of disparate biological pathways whose co-regulation drives the transcriptional coherence of their respective pathways. Overall, our data identifies transcriptional co-regulation of hundreds of discreet biological pathways and suggest that genomic clustering of their transacting factors such as transcription factors create operon-like regulation in eukaryotes.