Abstract
Genome-wide measurements of transcriptional activity in bacteria indicate that the transcription of successive genes is strongly correlated beyond the scale of operons. However, the underlying mechanisms are poorly characterized and a systematic method for identifying local groups of co-transcribed genes is lacking. Here, we identify supra-operonic segments of consecutive genes by comparing gene proximity in thousands of bacterial genomes. Structurally, the segments are contained within micro-domains delineated by known nucleoid-associated proteins, and they contain operons with specific relative orientations. Functionally, the operons within a same segment are highly co-transcribed, even in the absence of regulatory factors at their promoter regions. Hence, operons with no common regulatory factor can be co-regulated if they share a regulatory factor at the level of segments. To rationalize these findings, we put forward the hypothesis supported by RNA-seq data that facilitated co-transcription, the feedback of transcription into itself involving only DNA and RNA-polymerases, may represent both an evolutionary primitive and a functionally primary mode of gene regulation.