Chromosome position effects on gene expression in Escherichia coli K-12

Abstract

In eukaryotes, the location of a gene on the chromosome is known to affect its expression, but such position effects are poorly understood in bacteria. Here, using Escherichia coli K-12, we demonstrate that expression of a reporter gene cassette, comprised of the model E. coli lac promoter driving expression of gfp, varies by ∼300-fold depending on its precise position on the chromosome. At some positions, expression was more than 3-fold higher than at the natural lac promoter locus, whereas at several other locations, the reporter cassette was completely silenced: effectively overriding local lac promoter control. These effects were not due to differences in gene copy number, caused by partially replicated genomes. Rather, the differences in gene expression occur predominantly at the level of transcription and are mediated by several different features that are involved in chromosome organization. Taken together, our findings identify a tier of gene regulation above local promoter control and highlight the importance of chromosome position effects on gene expression profiles in bacteria.

Coevolution of the Organization and Structure of Prokaryotic Genomes

“…Recent data suggests that the organization of transcription at the genomic level is more plastic than previously thought because of frequent alternative transcription start sites (Cho et al 2009), chromosome structure (Bryant et al 2014), and supraoperonic organization Warren and ten Wolde 2004;Hershberg et al 2005). It is therefore possible that intraoperonic, operonic, and supraoperonic gene organization represent a continuum of scales of transcriptional organization.…”

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

“…Bioinformatic analyses and experimental work have indicated that gene location can affect expression for reasons other than gene dosage (i.e. because a gene near the origin of chromosome replication doubles its copy number earlier in the cell cycle than one near the replication terminus) and that part of the underlying reason reflects differences in DNA supercoiling at different chromosomal sites (Bryant et al 2014;Sobetzko et al 2012).…”

Why the activity of a gene depends on its neighbors

“…Because our arguments are general, our model should apply to any complex genome. Indeed, position effects have recently been found in bacteria [64], where highly-active genes divide the genome into domains [65,66] and a 3C-based technique shows co-regulated operons cluster in 3D space [61]. Then, the words of Lewis were prescient: position determines '...the organization of the chromosomes as well as...the primary reactions of specific genes'.…”