In contrast to the core polymerase (α2ββ'), the RNA polymerase holoenzyme (α2ββ'σ) can use intact DNA as a template for RNA synthesis. Transcription begins when the holoenzyme recognizes and binds to specific initiation signals called promoters at the beginning of a transcription unit. The existence of promoters was first demonstrated by isolation of a particular class of mutations in E. coli that prevent cells from synthesizing enzymes required for lactose metabolism. These mutations, termed promoter mutations, not only result in a lack of gene activity but also cannot be complemented because they are cis-dominant.

    Sigma factor is essential for promoter DNA recognition but does not bind to promoter DNA on its own. The major E. coli σ factor, called σ⁷⁰ because its molecular mass is about 70 kDa, helps core polymerase to bind to promoters in genes that code for housekeeping enzymes (enzymes required for essential metabolic steps in the cell)and destabilizes nonspecific interactions between RNA polymerase and DNA. Other bacterial species have σ⁷⁰ homologs that perform the same function. The fact that core RNA polymerase can transcribe nicked DNA but not intact DNA suggested that σ⁷⁰ might function by introducing transient nicks into DNA. Despite extensive efforts to observe such a nicking activity, none has ever been observed. For in-stance, σ⁷⁰ does not alter the linking number of supercoiled DNA.