Gene clustering drives the transcriptional coherence of disparate biological processes in eukaryotes

The establishment of distinct transcriptional states entails coordinated transcriptional coregulation of several functionally disparate biological processes (fd-BPs), involving thousands of genes scattered throughout the genome. Linear clustering of genes in a single BP is one strategy for their transcriptional coregulation. However, whether such gene clustering also plays a role in transcriptional coherence of several fd-BPs remains unexplored. Here, by analyzing the genomes of eukaryotes ranging from yeast to plants to humans, we find thousands of conserved and species-specific clustered fd-BP pairs, many of which are transcriptionally correlated in normal human tissues. Strikingly, our results reveal that often this system-level transcriptional coordination is achieved in part by the genic proximity of regulatory nodes of fd-BPs (such as transcription factors) whose coregulation drives the transcriptional coherence of their respective pathways. This, we hypothesize, is one strategy for creating coregulated, tunable modulons in eukaryotes.