Gene clustering coordinates transcriptional output of disparate biological processes in eukaryotes

Abstract

AbstractThe establishment of distinct transcriptional programs in response to developmental or environmental cues is central to all life. This entails the concordant and discordant transcriptional regulation of several distinct biological processes (BP) often involving thousands of genes. Genomic clustering of genes in a BP is one strategy by which transcriptional coregulation of a BP’s genes is achieved. However, whether gene clustering also plays a role in transcriptional coherence of several distinct BPs, often involving thousands of genes, remains unexplored. Here, by analyzing the genomes of eukaryotes ranging from yeast to human, we report the identification of thousands of conserved and species-specific discrete clustered BP pairs, many of which in normal human tissues are transcriptionally correlated. Strikingly, our results reveal that system-level transcriptional coordination is achieved in part by the genic proximity of regulatory nodes of disparate BPs whose coregulation drives the transcriptional coherence of their respective pathways. This, we hypothesize, is one strategy for creating coregulated, tunable modulons in eukaryotes.