Date Published: April 18, 2017
Publisher: Public Library of Science
Author(s): Lucia Pannier, Enrique Merino, Kathleen Marchal, Julio Collado-Vides, Akira Ishihama.
In prokaryotes, genomic distance is a feature that in addition to coregulation affects coexpression. Several observations, such as genomic clustering of highly coexpressed small regulons, support the idea that coexpression behavior of coregulated genes is affected by the distance between the coregulated genes. However, the specific contribution of distance in addition to coregulation in determining the degree of coexpression has not yet been studied systematically. In this work, we exploit the rich information in RegulonDB to study how the genomic distance between coregulated genes affects their degree of coexpression, measured by pairwise similarity of expression profiles obtained under a large number of conditions. We observed that, in general, coregulated genes display higher degrees of coexpression as they are more closely located on the genome. This contribution of genomic distance in determining the degree of coexpression was relatively small compared to the degree of coexpression that was determined by the tightness of the coregulation (degree of overlap of regulatory programs) but was shown to be evolutionary constrained. In addition, the distance effect was sufficient to guarantee coexpression of coregulated genes that are located at very short distances, irrespective of their tightness of coregulation. This is partly but definitely not always because the close distance is also the cause of the coregulation. In cases where it is not, we hypothesize that the effect of the distance on coexpression could be caused by the fact that coregulated genes closely located to each other are also relatively more equidistantly located from their common TF and therefore subject to more similar levels of TF molecules. The absolute genomic distance of the coregulated genes to their common TF-coding gene tends to be less important in determining the degree of coexpression. Our results pinpoint the importance of taking into account the combined effect of distance and coregulation when studying prokaryotic coexpression and transcriptional regulation.
Transcriptional coregulation in general implies coexpression: genes that are regulated by the same Transcription Factors (TFs) are more likely to be coexpressed. RegulonDB defines the transcriptional programs of genes in E. coli K-12 based on curated information. A distinction is often made between simple and complex transcriptional regulatory programs depending on whether a gene’s regulatory program consists of at most one or more TFs. Genes are defined to be coregulated if their respective regulatory program overlaps, i.e. if they are coregulated by at least one TF with the same role (activator, repressor or dual). The complexity of their individual regulatory programs in combination with the extent to which their program overlaps defines the tightness of the coregulation. Genes with a completely identical regulatory program are expected to be more tightly coregulated under all conditions than in case of an incomplete overlap. In the latter case different gene-specific TFs can be involved in tuning the expression at the individual gene level (less tight coregulation). Also if more TFs are shared by the coregulated genes, their coregulation can be expected to be tighter.
In prokaryotes, genomic distance is a feature that in addition to coregulation affects coexpression. In this work, we evaluated how the genomic distance of genes known to be coregulated in E. coli contributes to their coexpression behavior. Hereto, we combined information on regulation in E. coli K-12 reported in RegulonDB, one of the largest curated and continually updated transcriptional databases, with publicly available expression data. Based on the information available for E. coli K-12 we observed that in general coregulated genes display higher degrees of coexpression as they are more closely located on the genome.