Mycobacterial SigA and SigB Cotranscribe Essential Housekeeping Genes during Exponential Growth.

Mycobacterial σ belongs to the group II family of sigma factors, which are widely considered to transcribe genes required for stationary-phase survival and the response to stress. Here we explored the mechanism underlying the observed hypersensitivity of Δ deletion mutants of , , and to rifampin (RIF) and uncovered an additional constitutive role of σ during exponential growth of mycobacteria that complements the function of the primary sigma factor, σ Using chromatin immunoprecipitation sequencing (ChIP-Seq), we show that during exponential phase, σ binds to over 200 promoter regions, including those driving expression of essential housekeeping genes, like the rRNA gene. ChIP-Seq of ectopically expressed σ-FLAG demonstrated that at least 61 promoter sites are recognized by both σ and σ These results together suggest that RNA polymerase holoenzymes containing either σ or σ transcribe housekeeping genes in exponentially growing mycobacteria. The RIF sensitivity of the Δ mutant possibly reflects a decrease in the effective housekeeping holoenzyme pool, which results in susceptibility of the mutant to lower doses of RIF. Consistent with this model, overexpression of σ restores the RIF tolerance of the Δ mutant to that of the wild type, concomitantly ruling out a specialized role of σ in RIF tolerance. Although the properties of mycobacterial σ parallel those of σ in its ability to transcribe a subset of housekeeping genes, σ presents a clear departure from the paradigm, wherein the cellular levels of σ are tightly controlled during exponential growth, such that the transcription of housekeeping genes is initiated exclusively by a holoenzyme containing σ (E.σ). All mycobacteria encode a group II sigma factor, σ, closely related to the group I principal housekeeping sigma factor, σ Group II sigma factors are widely believed to play specialized roles in the general stress response and stationary-phase transition in the bacteria that encode them. Contrary to this widely accepted view, we show an additional housekeeping function of σ that complements the function of σ in logarithmically growing cells. These findings implicate a novel and dynamic partnership between σ and σ in maintaining the expression of housekeeping genes in mycobacteria and can perhaps be extended to other bacterial species that possess multiple group II sigma factors.