Sigma E of Streptomyces coelicolor can function both as a direct activator or repressor of transcription

Sigma factors are key components of the bacterial transcriptional apparatus that are essential for promoter recognition and transcription initiation. These factors are considered as positive regulators of gene expression. Here, we reveal the opposite, inhibitory role of these proteins. We used a combination of ChIP-seq, transcriptomic time series data, promoter sequence analysis, and computational modeling of gene expression to analyze the regulatory activity of the extracytoplasmic σE factor from Streptomyces coelicolor. Kinetic modeling of gene expression then allowed to cluster respective genes into groups, based on the type of their control. Importantly, this analysis indicated that σE might act not only as an activator of gene expression but also as its repressor. The direct repressor function of σE was then demonstrated by experimental analysis of selected promoter regions in vivo, showing that σE binds to promoter-like sequences, forming roadblocks for transcription initiated upstream. Finally, the σE interactome was defined, allowing the identification of ApgA as its potential anti- factor. Taken together, the results characterize σE, its regulation, regulon, and reveal its direct inhibitory function in gene expression, a so far unknown phenomenon that may be common also to other factors and organisms.