Sigma and RNA polymerase: an on-again, off-again relationship?

In bacteria, a fundamental level of gene regulation occurs by competitive association of promoter-specificity factors called sigmas with RNA polymerase (RNAP). This sigma cycle paradigm underpins much of our understanding of all transcriptional regulation. Here, we review recent challenges to the sigma cycle paradigm in the context of its essential features and of the structural basis of sigma interactions with RNAP and elongation complexes. Although sigmas can play dual roles as both initiation and elongation regulators, we suggest that the key postulate of the sigma cycle, that sigmas compete for binding to RNAP after each round of RNA synthesis, remains the central mechanism for programming transcription initiation in bacteria.